{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:50:34Z","timestamp":1792497034174,"version":"4.5.0"},"reference-count":199,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["219366\/Z\/19\/Z"],"award-info":[{"award-number":["219366\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["740427 BrainEnergy"],"award-info":[{"award-number":["740427 BrainEnergy"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["LIDo PhD studentship"],"award-info":[{"award-number":["LIDo PhD studentship"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001320","name":"Wolfson Foundation","doi-asserted-by":"publisher","award":["LWENC PhD studentship"],"award-info":[{"award-number":["LWENC PhD studentship"]}],"id":[{"id":"10.13039\/501100001320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Therapies targeting late events in Alzheimer\u2019s disease (AD), including aggregation of amyloid beta (A\u03b2) and hyperphosphorylated tau, have largely failed, probably because they are given after significant neuronal damage has occurred. Biomarkers suggest that the earliest event in AD is a decrease of cerebral blood flow (CBF). This is caused by constriction of capillaries by contractile pericytes, probably evoked by oligomeric A\u03b2. CBF is also reduced by neutrophil trapping in capillaries and clot formation, perhaps secondary to the capillary constriction. The fall in CBF potentiates neurodegeneration by upregulating the BACE1 enzyme that makes A\u03b2 and by promoting tau hyperphosphorylation. Surprisingly, therefore, CBF reduction may play a crucial role in driving cognitive decline by initiating the amyloid cascade itself, or being caused by and amplifying A\u03b2 production. Here, we review developments in this area that are neglected in current approaches to AD, with the aim of promoting novel mechanism-based therapeutic approaches.<\/jats:p>","DOI":"10.1007\/s00401-020-02215-w","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T15:04:03Z","timestamp":1598886243000},"page":"793-810","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":332,"title":["Cerebral blood flow decrease as an early pathological mechanism in Alzheimer's disease"],"prefix":"10.1007","volume":"140","author":[{"given":"Nils","family":"Korte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Nortley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3618-0843","authenticated-orcid":false,"given":"David","family":"Attwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"2215_CR1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3389\/fneur.2020.00149","volume":"11","author":"L Abdullah","year":"2020","unstructured":"Abdullah L, Crawford F, Tsolaki M, B\u00f6rjesson-Hanson A, Olde Rikkert M, Pasquier F et al (2020) The Influence of baseline Alzheimer\u2019s disease severity on cognitive decline and CSF biomarkers in the NILVAD trial. Front Neurol 11:149. https:\/\/doi.org\/10.3389\/fneur.2020.00149","journal-title":"Front Neurol"},{"key":"2215_CR2","doi-asserted-by":"publisher","first-page":"91003","DOI":"10.1115\/1.4030824","volume":"137","author":"ML Akenhead","year":"2015","unstructured":"Akenhead ML, Horrall NM, Rowe D, Sethu P, Shin HY (2015) In vitro evaluation of the link between cell activation state and its rheological Impact on the microscale flow of neutrophil suspensions. J Biomech Eng 137:91003. https:\/\/doi.org\/10.1115\/1.4030824","journal-title":"J Biomech Eng"},{"key":"2215_CR3","doi-asserted-by":"publisher","first-page":"e34861","DOI":"10.7554\/eLife.34861.001","volume":"7","author":"L Alarcon-Martinez","year":"2018","unstructured":"Alarcon-Martinez L, Yilmaz-Ozcan S, Yemisci M, Schallek J, Kilic K, Can A et al (2018) Capillary pericytes express \u03b1-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection. Elife 7:e34861. https:\/\/doi.org\/10.7554\/eLife.34861.001","journal-title":"Elife"},{"key":"2215_CR4","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature09522","volume":"468","author":"A Armulik","year":"2010","unstructured":"Armulik A, Genov\u00e9 G, M\u00e4e M, Nisancioglu MH, Wallgard E, Niaudet C et al (2010) Pericytes regulate the blood-brain barrier. Nature 468:557\u2013561. https:\/\/doi.org\/10.1038\/nature09522","journal-title":"Nature"},{"key":"2215_CR5","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/sj.jcbfm.9600570","volume":"28","author":"I Asllani","year":"2008","unstructured":"Asllani I, Habeck C, Scarmeas N, Borogovac A, Brown TR, Stern Y (2008) Multivariate and univariate analysis of continuous arterial spin labeling perfusion MRI in Alzheimer\u2019s disease. J Cereb Blood Flow Metab 28:725\u2013736. https:\/\/doi.org\/10.1038\/sj.jcbfm.9600570","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR6","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1084\/jem.20142290","volume":"212","author":"A Aspelund","year":"2015","unstructured":"Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M et al (2015) A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med 212:991\u2013999. https:\/\/doi.org\/10.1084\/jem.20142290","journal-title":"J Exp Med"},{"key":"2215_CR7","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s00401-004-0822-6","volume":"107","author":"J Attems","year":"2004","unstructured":"Attems J, Lintner F, Jellinger KA (2004) Amyloid beta peptide 1\u201342 highly correlates with capillary cerebral amyloid angiopathy and Alzheimer disease pathology. Acta Neuropathol 107:283\u2013291. https:\/\/doi.org\/10.1007\/s00401-004-0822-6","journal-title":"Acta Neuropathol"},{"key":"2215_CR8","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1097\/00004647-200110000-00001","volume":"21","author":"D Attwell","year":"2001","unstructured":"Attwell D, Laughlin SB (2001) An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab 21:1133\u20131145. https:\/\/doi.org\/10.1097\/00004647-200110000-00001","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR9","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1177\/0271678X15610340","volume":"36","author":"D Attwell","year":"2016","unstructured":"Attwell D, Mishra A, Hall CN, O\u2019Farrell FM, Dalkara T (2016) What is a pericyte? J Cereb Blood Flow Metab 36:451\u2013455. https:\/\/doi.org\/10.1177\/0271678X15610340","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR10","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/nrd1330","volume":"3","author":"KJ Barnham","year":"2004","unstructured":"Barnham KJ, Masters CL, Bush CI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205\u2013214. https:\/\/doi.org\/10.1038\/nrd1330","journal-title":"Nat Rev Drug Discov"},{"key":"2215_CR11","doi-asserted-by":"publisher","first-page":"18008","DOI":"10.1523\/JNEUROSCI.1402-13.2013","volume":"33","author":"LL Beason-Held","year":"2013","unstructured":"Beason-Held LL, Goh JO, An Y, Kraut MA, O\u2019Brien RJ, Ferrucci L et al (2013) Changes in brain function occur years before the onset of cognitive impairment. J Neurosci 33:18008\u201318014. https:\/\/doi.org\/10.1523\/JNEUROSCI.1402-13.2013","journal-title":"J Neurosci"},{"key":"2215_CR12","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13024-017-0225-5","volume":"12","author":"K Belarbi","year":"2017","unstructured":"Belarbi K, Cuvelier E, Dest\u00e9e A, Gressier B, Chartier-Harlin M-C (2017) NADPH oxidases in Parkinson\u2019s disease: a systematic review. Mol Neurodegener 12:84. https:\/\/doi.org\/10.1186\/s13024-017-0225-5","journal-title":"Mol Neurodegener"},{"key":"2215_CR13","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.neuron.2010.09.043","volume":"68","author":"RD Bell","year":"2010","unstructured":"Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R et al (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68:409\u2013427. https:\/\/doi.org\/10.1016\/j.neuron.2010.09.043","journal-title":"Neuron"},{"key":"2215_CR14","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nchembio782","volume":"2","author":"DA Bosco","year":"2006","unstructured":"Bosco DA, Fowler DM, Zhang Q, Nieva J, Powers ET, Wentworth P et al (2006) Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate alpha-synuclein fibrilization. Nat Chem Biol 2:249\u2013253. https:\/\/doi.org\/10.1038\/nchembio782","journal-title":"Nat Chem Biol"},{"key":"2215_CR15","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1177\/0271678X19873658","volume":"40","author":"O Bracko","year":"2019","unstructured":"Bracko O, Njiru BN, Swallow M, Ali M, Haft-Javaherian M, Schaffer CB (2019) Increasing cerebral blood flow improves cognition into late stages in Alzheimer\u2019s disease mice. J Cereb Blood Flow Metab 40:1441\u20131452. https:\/\/doi.org\/10.1177\/0271678X19873658","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR16","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/0026-2862(84)90064-5","volume":"27","author":"M Braide","year":"1984","unstructured":"Braide M, Amundson B, Chien S, Bagge U (1984) Quantitative studies on the influence of leukocytes on the vascular resistance in a skeletal muscle preparation. Microvasc Res 27:331\u2013352. https:\/\/doi.org\/10.1016\/0026-2862(84)90064-5","journal-title":"Microvasc Res"},{"key":"2215_CR17","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1177\/0271678X19873658","volume":"3","author":"S Bressi","year":"1992","unstructured":"Bressi S, Volont\u00e8 M, Alberoni M, Canal N, Franceschi M (1992) Transcranial Doppler sonography in the early phase of Alzheimer\u2019s disease. Dement Geriatr Cogn Discord 3:25\u201331. https:\/\/doi.org\/10.1177\/0271678X19873658","journal-title":"Dement Geriatr Cogn Discord"},{"key":"2215_CR18","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1001\/archneurol.2012.1527","volume":"69","author":"AM Brickman","year":"2012","unstructured":"Brickman AM, Provenzano FA, Muraskin J, Manly JJ, Blum S, Apa Z et al (2012) Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community. Arch Neurol 69:1621\u20131627. https:\/\/doi.org\/10.1001\/archneurol.2012.1527","journal-title":"Arch Neurol"},{"key":"2215_CR19","doi-asserted-by":"publisher","first-page":"8740","DOI":"10.1073\/pnas.1206171109","volume":"109","author":"MA Busche","year":"2012","unstructured":"Busche MA, Chen X, Henning HA, Reichwald J, Staufenbiel M, Sakmann B et al (2012) Critical role of soluble amyloid-\u03b2 for early hippocampal hyperactivity in a mouse model of Alzheimer\u2019s disease. Proc Natl Acad Sci USA 109:8740\u20138745. https:\/\/doi.org\/10.1073\/pnas.1206171109","journal-title":"Proc Natl Acad Sci USA"},{"key":"2215_CR20","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1126\/science.1162844","volume":"321","author":"MA Busche","year":"2008","unstructured":"Busche MA, Eichhoff G, Adelsberger H, Abramowski D, Wiederhold K-H, Haass C et al (2008) Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer\u2019s disease. Science 321:1686\u20131689. https:\/\/doi.org\/10.1126\/science.1162844","journal-title":"Science"},{"key":"2215_CR21","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/s41593-018-0289-8","volume":"22","author":"MA Busche","year":"2019","unstructured":"Busche MA, Wegmann S, Dujardin S, Commins C, Schiantarelli J, Klickstein N et al (2019) Tau impairs neural circuits, dominating amyloid-\u03b2 effects, in Alzheimer models in vivo. Nat Neurosci 22:57\u201364. https:\/\/doi.org\/10.1038\/s41593-018-0289-8","journal-title":"Nat Neurosci"},{"key":"2215_CR22","doi-asserted-by":"publisher","first-page":"14208","DOI":"10.1074\/jbc.M114.625251","volume":"290","author":"CS Casey","year":"2015","unstructured":"Casey CS, Atagi Y, Yamazaki Y, Shinohara M, Tachibana M, Fu Y et al (2015) Apolipoprotein E inhibits cerebrovascular motility through a RhoA protein-mediated pathway. JBiol Chem 290:14208\u201314217. https:\/\/doi.org\/10.1074\/jbc.M114.625251","journal-title":"JBiol Chem"},{"key":"2215_CR23","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.ajpath.2013.10.002","volume":"184","author":"X Cheng","year":"2014","unstructured":"Cheng X, He P, Lee T, Yao H, Li R, Shen Y (2014) High activities of BACE1 in brains with mild cognitive impairment. Am J Pathol 184:141\u2013147. https:\/\/doi.org\/10.1016\/j.ajpath.2013.10.002","journal-title":"Am J Pathol"},{"key":"2215_CR24","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40478-014-0083-0","volume":"2","author":"LE Collins-Praino","year":"2014","unstructured":"Collins-Praino LE, Francis YI, Griffith EY, Wiegman AF, Urbach J, Lawton A et al (2014) Soluble amyloid beta levels are elevated in the white matter of Alzheimer\u2019s patients, independent of cortical plaque severity. Acta Neuropathol Commun 2:83. https:\/\/doi.org\/10.1186\/s40478-014-0083-0","journal-title":"Acta Neuropathol Commun"},{"key":"2215_CR25","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1016\/j.jacc.2019.07.081","volume":"74","author":"M Cortes-Canteli","year":"2019","unstructured":"Cortes-Canteli M, Kruyer A, Fernandez-Nueda I, Marcos-Diaz A, Ceron C, Richards AT et al (2019) Long-term dabigatran treatment delays Alzheimer\u2019s disease pathogenesis in the TgCRND8 mouse model. J Am Coll Cardiol 74:1910\u20131923. https:\/\/doi.org\/10.1016\/j.jacc.2019.07.081","journal-title":"J Am Coll Cardiol"},{"key":"2215_CR26","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/s41593-018-0329-4","volume":"22","author":"JC Cruz Hern\u00e1ndez","year":"2019","unstructured":"Cruz Hern\u00e1ndez JC, Bracko O, Kersbergen CJ, Muse V, Haft-Javaherian M, Berg M et al (2019) Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer\u2019s disease mouse models. Nat Neurosci 22:413\u2013420. https:\/\/doi.org\/10.1038\/s41593-018-0329-4","journal-title":"Nat Neurosci"},{"key":"2215_CR27","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1161\/STROKEAHA.107.495457","volume":"39","author":"W Dai","year":"2008","unstructured":"Dai W, Lopez OL, Carmichael OT, Becker JT, Kuller LH, Gach HM (2008) Abnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension. Stroke 39:349\u2013354. https:\/\/doi.org\/10.1161\/STROKEAHA.107.495457","journal-title":"Stroke"},{"key":"2215_CR28","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41586-018-0368-8","volume":"560","author":"S Da Mesquita","year":"2018","unstructured":"Da Mesquita S, Louveau A, Vaccari A, Smirnov I, Cornelison RC, Kingsmore KM et al (2018) Functional aspects of meningeal lymphatics in ageing and Alzheimer\u2019s disease. Nature 560:185\u2013191. https:\/\/doi.org\/10.1038\/s41586-018-0368-8","journal-title":"Nature"},{"key":"2215_CR29","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1161\/HYPERTENSIONAHA.119.12892","volume":"74","author":"DLK de Jong","year":"2019","unstructured":"de Jong DLK, de Heus RAA, Rijpma A, Donders R, Olde Rikkert MGM, G\u00fcnther M et al (2019) Effects of nilvadipine on cerebral blood flow in patients With Alzheimer disease. Hypertension 74:413\u2013420. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.119.12892","journal-title":"Hypertension"},{"key":"2215_CR30","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1002\/ana.410250506","volume":"25","author":"SM de la Monte","year":"1989","unstructured":"de la Monte SM (1989) Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer\u2019s disease. Ann Neurol 25:450\u2013459. https:\/\/doi.org\/10.1002\/ana.410250506","journal-title":"Ann Neurol"},{"key":"2215_CR31","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1080\/01616412.1993.11740127","volume":"15","author":"JC de la Torre","year":"1993","unstructured":"de la Torre JC, Mussivand T (1993) Can disturbed brain microcirculation cause Alzheimer\u2019s disease? Neurol Res 15:146\u2013153. https:\/\/doi.org\/10.1080\/01616412.1993.11740127","journal-title":"Neurol Res"},{"key":"2215_CR32","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/nm890","volume":"9","author":"R Deane","year":"2003","unstructured":"Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E et al (2003) RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9:907\u2013913. https:\/\/doi.org\/10.1038\/nm890","journal-title":"Nat Med"},{"key":"2215_CR33","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/ana.25749","volume":"88","author":"RA Desai","year":"2020","unstructured":"Desai RA, Davies AL, Del Rossi N, Tachrount M, Dyson A, Gustavson B et al (2020) Nimodipine reduces dysfunction and demyelination in models of multiple sclerosis. Ann Neurol 88:123\u2013136. https:\/\/doi.org\/10.1002\/ana.25749","journal-title":"Ann Neurol"},{"key":"2215_CR34","doi-asserted-by":"publisher","first-page":"5654","DOI":"10.1073\/pnas.1222560110","volume":"110","author":"M D\u2019haeseleer","year":"2013","unstructured":"D\u2019haeseleer M, Beelen R, Fierens Y, Cambron M, Vanbinst AM, Verborgh C et al (2013) Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1. Proc Natl Acad Sci USA 110:5654\u20135658. https:\/\/doi.org\/10.1073\/pnas.1222560110","journal-title":"Proc Natl Acad Sci USA"},{"key":"2215_CR35","doi-asserted-by":"publisher","first-page":"e12005","DOI":"10.1002\/dad2.12005","volume":"12","author":"K Dhiman","year":"2020","unstructured":"Dhiman K, Gupta VB, Villemagne VL, Eratne D, Graham PL, Fowler C et al (2020) Cerebrospinal fluid neurofilament light concentration predicts brain atrophy and cognition in Alzheimer\u2019s disease. Alzheimers Dement 12:e12005. https:\/\/doi.org\/10.1002\/dad2.12005","journal-title":"Alzheimers Dement"},{"key":"2215_CR36","doi-asserted-by":"publisher","first-page":"475","DOI":"10.3389\/fnins.2017.00475","volume":"11","author":"AK Diem","year":"2017","unstructured":"Diem AK, MacGregor Sharp M, Gatherer M, Bressloff NW, Carare RO, Richardson G (2017) Arterial pulsations cannot drive intramural periarterial drainage: significance for A\u03b2 drainage. Front Neurosci 11:475. https:\/\/doi.org\/10.3389\/fnins.2017.00475","journal-title":"Front Neurosci"},{"key":"2215_CR37","doi-asserted-by":"publisher","first-page":"H314","DOI":"10.1152\/ajpheart.1986.251.2.H314","volume":"251","author":"RL Engler","year":"1986","unstructured":"Engler RL, Dahlgren MD, Morris DD, Peterson MA, Schmid-Sch\u00f6nbein GW (1986) Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. Am J Physiol 251:H314\u2013323. https:\/\/doi.org\/10.1152\/ajpheart.1986.251.2.H314","journal-title":"Am J Physiol"},{"key":"2215_CR38","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.neurobiolaging.2016.11.004","volume":"50","author":"SF Eskildsen","year":"2017","unstructured":"Eskildsen SF, Gyldensted L, Nagenthiraja K, Nielsen RB, Hansen MB, Dalby RB et al (2017) Increased cortical capillary transit time heterogeneity in Alzheimer\u2019s disease: a DSC-MRI perfusion study. Neurobiol Aging 50:107\u2013118. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2016.11.004","journal-title":"Neurobiol Aging"},{"key":"2215_CR39","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/ana.23748","volume":"73","author":"TJ Esparza","year":"2013","unstructured":"Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM et al (2013) Amyloid-\u03b2 oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol 73:104\u2013119. https:\/\/doi.org\/10.1002\/ana.23748","journal-title":"Ann Neurol"},{"key":"2215_CR40","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1002\/jmri.26810","volume":"51","author":"A Fazlollahi","year":"2020","unstructured":"Fazlollahi A, Calamante F, Liang X, Bourgeat P, Raniga P, Dore V et al (2020) Increased cerebral blood flow with increased amyloid burden in the preclinical phase of Alzheimer\u2019s disease. J Magn Reson Imaging 51:505\u2013513. https:\/\/doi.org\/10.1002\/jmri.26810","journal-title":"J Magn Reson Imaging"},{"key":"2215_CR41","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/jcbfm.2012.187","volume":"33","author":"F Fernandez-Klett","year":"2013","unstructured":"Fernandez-Klett F, Potas JR, Hilpert D, Blazej K, Radke J, Huck J et al (2013) Early loss of pericytes and perivascular stromal cell-induced scar formation after stroke. J Cereb Blood Flow Metab 33:428\u2013439. https:\/\/doi.org\/10.1038\/jcbfm.2012.187","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR42","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/S1053-8119(03)00364-1","volume":"20","author":"MJ Firbank","year":"2003","unstructured":"Firbank MJ, Colloby SJ, Burn DJ, McKeith IG, O\u2019Brien JT (2003) Regional cerebral blood flow in Parkinson\u2019s disease with and without dementia. Neuroimage 20:1309\u20131319. https:\/\/doi.org\/10.1016\/S1053-8119(03)00364-1","journal-title":"Neuroimage"},{"key":"2215_CR43","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/0006-8993(90)90560-X","volume":"509","author":"JC Fowler","year":"1990","unstructured":"Fowler JC (1990) Adenosine antagonists alter the synaptic response to in vitro ischemia in the rat hippocampus. Brain Res 509:331\u2013334. https:\/\/doi.org\/10.1016\/0006-8993(90)90560-X","journal-title":"Brain Res"},{"key":"2215_CR44","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1093\/eurheartj\/ehx579","volume":"39","author":"L Friberg","year":"2018","unstructured":"Friberg L, Rosenqvist M (2018) Less dementia with oral anticoagulation in atrial fibrillation. Eur Heart J 39:453\u2013460. https:\/\/doi.org\/10.1093\/eurheartj\/ehx579","journal-title":"Eur Heart J"},{"key":"2215_CR45","doi-asserted-by":"publisher","first-page":"H1124","DOI":"10.1152\/ajpheart.00776.2018","volume":"316","author":"GA Fulop","year":"2019","unstructured":"Fulop GA, Tarantini S, Yabluchanskiy A, Molnar A, Prodan CI, Kiss T et al (2019) Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment. Am J Physiol Heart Circ Physiol 316:H1124\u2013H1140. https:\/\/doi.org\/10.1152\/ajpheart.00776.2018","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2215_CR46","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.1093\/brain\/awr300","volume":"134","author":"M Garcia-Alloza","year":"2011","unstructured":"Garcia-Alloza M, Gregory J, Kuchibhotla JV, Fine S, Wei Y, Ayata C et al (2011) Cerebrovascular lesions induce transient \u03b2-amyloid deposition. Brain 134:3697\u20133707. https:\/\/doi.org\/10.1093\/brain\/awr300","journal-title":"Brain"},{"key":"2215_CR47","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1016\/S0140-6736(16)31275-2","volume":"388","author":"S Gauthier","year":"2016","unstructured":"Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH et al (2016) Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer\u2019s disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 388:2873\u20132884. https:\/\/doi.org\/10.1016\/S0140-6736(16)31275-2","journal-title":"Lancet"},{"key":"2215_CR48","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1152\/japplphysiol.00966.2005","volume":"100","author":"H Girouard","year":"2006","unstructured":"Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 100:328\u2013335. https:\/\/doi.org\/10.1152\/japplphysiol.00966.2005","journal-title":"J Appl Physiol"},{"key":"2215_CR49","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1177\/0271678X16671146","volume":"37","author":"IG Gould","year":"2017","unstructured":"Gould IG, Tsai P, Kleinfeld D, Linninger A (2017) The capillary bed offers the largest hemodynamic resistance to the cortical blood supply. J Cereb Blood Flow Metab 37:52\u201368. https:\/\/doi.org\/10.1177\/0271678X16671146","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR50","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41582-019-0281-2","volume":"16","author":"SM Greenberg","year":"2020","unstructured":"Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, van Velew SJ (2020) Cerebral amyloid angiopathy and Alzheimer disease\u2014one peptide, two pathways. Nat Rev Neurol 16:30\u201342. https:\/\/doi.org\/10.1038\/s41582-019-0281-2","journal-title":"Nat Rev Neurol"},{"key":"2215_CR51","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1161\/STROKEAHA.117.016990","volume":"49","author":"SM Greenberg","year":"2018","unstructured":"Greenberg SM, Charidimou A (2018) Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. Stroke 49:491\u2013497. https:\/\/doi.org\/10.1161\/STROKEAHA.117.016990","journal-title":"Stroke"},{"key":"2215_CR52","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s00401-017-1707-9","volume":"133","author":"T Guo","year":"2017","unstructured":"Guo T, Noble W, Hanger DP (2017) Roles of tau protein in health and disease. Acta Neuropathol 133:665\u2013704. https:\/\/doi.org\/10.1007\/s00401-017-1707-9","journal-title":"Acta Neuropathol"},{"key":"2215_CR53","doi-asserted-by":"publisher","first-page":"3045","DOI":"10.3892\/mmr.2019.9950","volume":"19","author":"Y Guo","year":"2019","unstructured":"Guo Y, Li X, Zhang M, Chen N, Wu S, Lei J et al (2019) Age- and brain region-associated alterations of cerebral blood flow in early Alzheimer\u2019s disease assessed in A\u03b2PPSWE\/PS1\u0394E9 transgenic mice using arterial spin labeling. Mol Med Rep 19:3045\u20133052. https:\/\/doi.org\/10.3892\/mmr.2019.9950","journal-title":"Mol Med Rep"},{"key":"2215_CR54","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.neurobiolaging.2017.10.006","volume":"62","author":"E Guti\u00e9rrez-Jim\u00e9nez","year":"2018","unstructured":"Guti\u00e9rrez-Jim\u00e9nez E, Angleys H, Rasmussen PM, West MJ, Catalini L, Iversen NK et al (2018) Disturbances in the control of capillary flow in an aged APPswe\/PS1\u0394E9 model of Alzheimer\u2019s disease. Neurobiol Aging 62:82\u201394. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2017.10.006","journal-title":"Neurobiol Aging"},{"key":"2215_CR55","doi-asserted-by":"publisher","first-page":"e0213539","DOI":"10.1371\/journal.pone.0213539","volume":"14","author":"M Haft-Javaherian","year":"2019","unstructured":"Haft-Javaherian M, Fang L, Muse V, Schaffer CB, Nishimura N, Sabuncu MR (2019) Deep convolutional neural networks for segmenting 3D in vivo multiphoton images of vasculature in Alzheimer disease mouse models. PLoS ONE 14:e0213539. https:\/\/doi.org\/10.1371\/journal.pone.0213539","journal-title":"PLoS ONE"},{"key":"2215_CR56","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nature13165","volume":"508","author":"CN Hall","year":"2014","unstructured":"Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA et al (2014) Capillary pericytes regulate cerebral blood flow in health and disease. Nature 508:55\u201360. https:\/\/doi.org\/10.1038\/nature13165","journal-title":"Nature"},{"key":"2215_CR57","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1001\/jamaneurol.2019.1424","volume":"76","author":"BJ Hanseeuw","year":"2019","unstructured":"Hanseeuw BJ, Betensky RA, Jacobs HIL, Schultz AP, Sepulcre J, Becker JA et al (2019) Association of amyloid and tau with cognition in preclinical Alzheimer disease: a longitudinal study. JAMA Neurol 76:915\u2013924. https:\/\/doi.org\/10.1001\/jamaneurol.2019.1424","journal-title":"JAMA Neurol"},{"key":"2215_CR58","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.neurobiolaging.2019.06.009","volume":"82","author":"GK Hansra","year":"2019","unstructured":"Hansra GK, Popov G, Banaczek PO, Vogiatzis M, Jegathees T, Goldbury CS et al (2019) The neuritic plaque in Alzheimer\u2019s disease: perivascular degeneration of neuronal processes. Neurobiol Aging 82:88\u2013101. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2019.06.009","journal-title":"Neurobiol Aging"},{"key":"2215_CR59","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1126\/science.1566067","volume":"256","author":"JA Hardy","year":"1992","unstructured":"Hardy JA, Higgins GA (1992) Alzheimer\u2019s disease: the amyloid cascade hypothesis. Science 256:184\u2013185. https:\/\/doi.org\/10.1126\/science.1566067","journal-title":"Science"},{"key":"2215_CR60","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1046\/j.1460-9568.2000.00164.x","volume":"12","author":"T Harkany","year":"2000","unstructured":"Harkany T, Abrah\u00e1m I, Timmerman W, Laskay G, T\u00f3th B, Sasv\u00e1ri M et al (2000) beta-amyloid neurotoxicity is mediated by a glutamate-triggered excitotoxic cascade in rat nucleus basalis. Eur J Neurosci 12:2735\u20132745. https:\/\/doi.org\/10.1046\/j.1460-9568.2000.00164.x","journal-title":"Eur J Neurosci"},{"key":"2215_CR61","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s40478-019-0666-x","volume":"7","author":"Y Hase","year":"2019","unstructured":"Hase Y, Ding R, Harrison G, Hawthorne E, King A, Gettings S et al (2019) White matter capillaries in vascular and neurodegenerative dementias. Acta Neuropathol Commun 7:16. https:\/\/doi.org\/10.1186\/s40478-019-0666-x","journal-title":"Acta Neuropathol Commun"},{"key":"2215_CR62","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/nm.4443","volume":"24","author":"Z He","year":"2018","unstructured":"He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L et al (2018) Amyloid-\u03b2 plaques enhance Alzheimer\u2019s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 24:29\u201338. https:\/\/doi.org\/10.1038\/nm.4443","journal-title":"Nat Med"},{"key":"2215_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-019-0483-4","author":"S Hijazi","year":"2019","unstructured":"Hijazi S, Heistek TS, Scheltens P, Neumann U, Shimshek DR, Mansvelder HD et al (2019) Early restoration of parvalbumin interneuron activity prevents memory loss and network hyperexcitability in a mouse model of Alzheimer\u2019s disease. Mol Psychiatry. https:\/\/doi.org\/10.1038\/s41380-019-0483-4. (Online ahead of print)","journal-title":"Mol Psychiatry"},{"key":"2215_CR64","unstructured":"Hilal-Dandan R, Villegas S, Gonzalez A, Brunton LL (1997) The quasi-irreversible nature of endothelin binding and G protein-linked signaling in cardiac myocytes. J Pharmacol Exp Ther 281:267\u2013273. https:\/\/jpet.aspetjournals.org\/content\/jpet\/281\/1\/267.full.pdf. Accessed 20 Aug 2020"},{"key":"2215_CR65","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.neuron.2015.06.001","volume":"87","author":"RA Hill","year":"2015","unstructured":"Hill RA, Tong L, Yuan P, Murikinati S, Gupta S, Grutzendler J (2015) Regional blood flow in the normal and ischemic brain is controlled by arteriolar smooth muscle cell contractility and not by capillary pericytes. Neuron 87:95\u2013110. https:\/\/doi.org\/10.1016\/j.neuron.2015.06.001","journal-title":"Neuron"},{"key":"2215_CR66","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12987-018-0113-6","volume":"15","author":"SB Hladky","year":"2018","unstructured":"Hladky SB, Barrand MA (2018) Elimination of substances from the brain parenchyma: efflux via perivascular pathways and via the blood-brain barrier. Fluids Barriers CNS 15:30. https:\/\/doi.org\/10.1186\/s12987-018-0113-6","journal-title":"Fluids Barriers CNS"},{"key":"2215_CR67","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1016\/j.neuron.2010.11.030","volume":"68","author":"BR Hoover","year":"2010","unstructured":"Hoover BR, Reed MN, Su J, Penrod RD, Kotilinek LA, Grant MK et al (2010) Tau mislocalization to dendritic spines mediates synaptic dysfunction independently of neurodegeneration. Neuron 68:1067\u20131081. https:\/\/doi.org\/10.1016\/j.neuron.2010.11.030","journal-title":"Neuron"},{"key":"2215_CR68","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41582-019-0295-9","volume":"16","author":"R Howard","year":"2020","unstructured":"Howard R, Liu KY (2020) Questions EMERGE as Biogen claims aducanumab turnaround. Nat Rev Neurol 16:63\u201364. https:\/\/doi.org\/10.1038\/s41582-019-0295-9","journal-title":"Nat Rev Neurol"},{"key":"2215_CR69","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2217\/nmt.14.53","volume":"5","author":"TM Hughes","year":"2015","unstructured":"Hughes TM, Craft S, Lopez OL (2015) Review of \u2018the potential role of arterial stiffness in the pathogenesis of Alzheimer\u2019s disease\u2019. Neurodegener Dis Manag 5:121\u2013135. https:\/\/doi.org\/10.2217\/nmt.14.53","journal-title":"Neurodegener Dis Manag"},{"key":"2215_CR70","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/nature20587","volume":"540","author":"HF Iaccarino","year":"2016","unstructured":"Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ et al (2016) Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540:230\u2013235. https:\/\/doi.org\/10.1038\/nature20587","journal-title":"Nature"},{"key":"2215_CR71","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nrn1387","volume":"5","author":"C Iadecola","year":"2004","unstructured":"Iadecola C (2004) Neurovascular regulation in the normal brain and in Alzheimer\u2019s disease. Nat Rev Neurosci 5:347\u2013360. https:\/\/doi.org\/10.1038\/nrn1387","journal-title":"Nat Rev Neurosci"},{"key":"2215_CR72","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1161\/CIRCRESAHA.118.313260","volume":"124","author":"C Iadecola","year":"2019","unstructured":"Iadecola C, Gottesman RF (2019) Neurovascular and cognitive dysfunction in hypertension. Circ Res 124:1025\u20131044. https:\/\/doi.org\/10.1161\/CIRCRESAHA.118.313260","journal-title":"Circ Res"},{"key":"2215_CR73","doi-asserted-by":"publisher","first-page":"147ra111","DOI":"10.1126\/scitranslmed.3003748","volume":"4","author":"JJ Iliff","year":"2012","unstructured":"Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA et al (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid \u03b2. Sci Transl Med 4:147ra111. https:\/\/doi.org\/10.1126\/scitranslmed.3003748","journal-title":"Sci Transl Med"},{"key":"2215_CR74","doi-asserted-by":"publisher","first-page":"18190","DOI":"10.1523\/JNEUROSCI.1592-13.2013","volume":"33","author":"JJ Iliff","year":"2013","unstructured":"Iliff JJ, Wang M, Zeppenfeld DM, Venkataraman A, Plog BA, Liao Y et al (2013) Cerebral arterial pulsation drives paravascular CSF-interstitial fluid exchange in the murine brain. J Neurosci 33:18190\u201318199. https:\/\/doi.org\/10.1523\/JNEUROSCI.1592-13.2013","journal-title":"J Neurosci"},{"key":"2215_CR75","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1111\/j.1471-4159.2010.06708.x","volume":"113","author":"S Ito","year":"2010","unstructured":"Ito S, Ueno T, Ohtsuki S, Terasaki T (2010) Lack of brain-to-blood efflux transport activity of low-density lipoprotein receptor-related protein-1 (LRP-1) for amyloid-beta peptide(1\u201340) in mouse: involvement of an LRP-1-independent pathway. J Neurochem 113:1356\u20131363. https:\/\/doi.org\/10.1111\/j.1471-4159.2010.06708.x","journal-title":"J Neurochem"},{"key":"2215_CR76","doi-asserted-by":"publisher","first-page":"11934","DOI":"10.1038\/ncomms11934","volume":"7","author":"Y Iturria-Medina","year":"2016","unstructured":"Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-P\u00e9rez JM, Evans AC, Alzheimer\u2019s Disease Neuroimaging Initiative (2016) Early role of vascular dysregulation on late-onset Alzheimer\u2019s disease based on multifactorial data-driven analysis. Nat Commun 7:11934. https:\/\/doi.org\/10.1038\/ncomms11934","journal-title":"Nat Commun"},{"key":"2215_CR77","doi-asserted-by":"publisher","first-page":"4749","DOI":"10.1038\/s41598-019-41363-2","volume":"9","author":"F Ji","year":"2019","unstructured":"Ji F, Pasternak O, Ng KK, Chong JSX, Liu S, Zhang L et al (2019) White matter microstructural abnormalities and default network degeneration are associated with early memory deficit in Alzheimer\u2019s disease continuum. Sci Rep 9:4749. https:\/\/doi.org\/10.1038\/s41598-019-41363-2","journal-title":"Sci Rep"},{"key":"2215_CR78","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1042\/bst20051096","volume":"33","author":"JA Johnston","year":"2005","unstructured":"Johnston JA, Liu WW, Todd SA, Coulson DT, Murphy S, Irvine GB et al (2005) Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer\u2019s disease. Biochem Soc Trans 33:1096\u20131100. https:\/\/doi.org\/10.1042\/bst20051096","journal-title":"Biochem Soc Trans"},{"key":"2215_CR79","doi-asserted-by":"publisher","first-page":"19276","DOI":"10.1523\/JNEUROSCI.3487-13.2013","volume":"33","author":"T Kanekiyo","year":"2013","unstructured":"Kanekiyo T, Cirrito JR, Liu C-C, Shinohara M, Li J, Schuler DR et al (2013) Neuronal clearance of amyloid-\u03b2 by endocytic receptor LRP1. J Neurosci 33:19276\u201319283","journal-title":"J Neurosci"},{"key":"2215_CR80","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1097\/00002093-199100540-00002","volume":"5","author":"J Kawamura","year":"1991","unstructured":"Kawamura J, Meyer JS, Terayama Y, Weathers S (1991) Cerebral white matter perfusion in dementia of Alzheimer type. Alzheimer Dis Assoc Disord 5:231\u2013239. https:\/\/doi.org\/10.1097\/00002093-199100540-00002","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2215_CR81","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/0304-3940(95)11270-7","volume":"186","author":"AM Kennedy","year":"1995","unstructured":"Kennedy AM, Frackowiak RS, Newman SK, Bloomfield PM, Seaward J, Roques P et al (1995) Deficits in cerebral glucose metabolism demonstrated by positron emission tomography in individuals at risk of familial Alzheimer\u2019s disease. Neurosci Lett 186:17\u201320. https:\/\/doi.org\/10.1016\/0304-3940(95)11270-7","journal-title":"Neurosci Lett"},{"key":"2215_CR82","doi-asserted-by":"publisher","first-page":"2032","DOI":"10.1093\/brain\/awy143","volume":"141","author":"L Khennouf","year":"2018","unstructured":"Khennouf L, Gesslein B, Brazhe A, Octeau JC, Kutuzov N, Khakh BS et al (2018) Active role of capillary pericytes during stimulation-induced activity and spreading depolarization. Brain 141:2032\u20132046. https:\/\/doi.org\/10.1093\/brain\/awy143","journal-title":"Brain"},{"key":"2215_CR83","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1111\/j.1440-1819.1991.tb01189.x","volume":"45","author":"T Kimura","year":"1991","unstructured":"Kimura T, Hashimura T, Miyakawa T (1991) Observations of microvessels in the brain with Alzheimer\u2019s disease by the scanning electron microscopy. Jpn J Psychiatry Neurol 45:671\u2013676. https:\/\/doi.org\/10.1111\/j.1440-1819.1991.tb01189.x","journal-title":"Jpn J Psychiatry Neurol"},{"key":"2215_CR84","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/nn.4489","volume":"20","author":"K Kisler","year":"2017","unstructured":"Kisler K, Nelson AR, Rege SV, Ramanathan A, Wang Y, Ahuja A et al (2017) Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain. Nat Neurosci 20:406\u2013416. https:\/\/doi.org\/10.1038\/nn.4489","journal-title":"Nat Neurosci"},{"key":"2215_CR85","doi-asserted-by":"publisher","first-page":"1837","DOI":"10.15252\/embj.201796516","volume":"36","author":"G Kleinberger","year":"2017","unstructured":"Kleinberger G, Brendel M, Mracsko E, Wefers B, Groeneweg L, Xiang X et al (2017) The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism. EMBO J 36:1837\u20131853. https:\/\/doi.org\/10.15252\/embj.201796516","journal-title":"EMBO J"},{"issue":"Suppl 1","key":"2215_CR86","doi-asserted-by":"publisher","first-page":"S204","DOI":"10.1016\/j.neuroimage.2010.06.020","volume":"54","author":"M Koronyo-Hamaoui","year":"2011","unstructured":"Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, Miller CA, Ko MK, Black KL et al (2011) Identification of amyloid plaques in retinas from Alzheimer\u2019s patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage 54(Suppl 1):S204\u2013217. https:\/\/doi.org\/10.1016\/j.neuroimage.2010.06.020","journal-title":"Neuroimage"},{"key":"2215_CR87","unstructured":"Krogh A (1920) Nobel Lecture. www.nobelprize.org\/prizes\/medicine\/1920\/krogh\/lecture\/."},{"key":"2215_CR88","doi-asserted-by":"publisher","first-page":"585","DOI":"10.3233\/jad-190013","volume":"69","author":"S Kwon","year":"2019","unstructured":"Kwon S, Moreno-Gonzalez I, Taylor-Presse K, Edwards Iii G, Gamez N, Calderon O et al (2019) Impaired peripheral lymphatic function and cerebrospinal fluid outflow in a mouse model of Alzheimer\u2019s disease. J Alzheimers Dis 69:585\u2013593. https:\/\/doi.org\/10.3233\/jad-190013","journal-title":"J Alzheimers Dis"},{"key":"2215_CR89","doi-asserted-by":"publisher","first-page":"6448","DOI":"10.1073\/pnas.95.11.6448","volume":"95","author":"MP Lambert","year":"1998","unstructured":"Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M et al (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc Natl Acad Sci, USA 95:6448\u20136453. https:\/\/doi.org\/10.1073\/pnas.95.11.6448","journal-title":"Proc Natl Acad Sci, USA"},{"key":"2215_CR90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2174\/0929867327666200312114223","volume":"27","author":"CSW Law","year":"2020","unstructured":"Law CSW, Yeong KY (2020) Repurposing antihypertensive drugs for the management of Alzheimer\u2019s disease. Curr Med Chem 27:1\u201315. https:\/\/doi.org\/10.2174\/0929867327666200312114223","journal-title":"Curr Med Chem"},{"key":"2215_CR91","doi-asserted-by":"publisher","first-page":"127","DOI":"10.3233\/jad-2003-5207","volume":"5","author":"M-S Lee","year":"2003","unstructured":"Lee M-S, Tsai L-H (2003) Cdk5: one of the links between senile plaques and neurofibrillary tangles? J Alzheimers Dis 5:127\u2013137. https:\/\/doi.org\/10.3233\/jad-2003-5207","journal-title":"J Alzheimers Dis"},{"key":"2215_CR92","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.nbd.2015.10.019","volume":"85","author":"M Lei","year":"2016","unstructured":"Lei M, Xu H, Li Z, Wang Z, O\u2019Malley TT, Zhang D et al (2016) Soluble A\u03b2 oligomers impair hippocampal LTP by disrupting glutamatergic\/GABAergic balance. Neurobiol Dis 85:111\u2013121. https:\/\/doi.org\/10.1016\/j.nbd.2015.10.019","journal-title":"Neurobiol Dis"},{"key":"2215_CR93","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.2147\/ndt.s207069","volume":"15","author":"R-R Li","year":"2019","unstructured":"Li R-R, He Y-S, Liu M, Nie Z-Y, Huang L-H, Lu Z et al (2019) Analysis of correlation between cerebral perfusion and KIM score of white matter lesions in patients with Alzheimer\u2019s disease. Neuropsychiatr Dis Treat 15:2705\u20132714. https:\/\/doi.org\/10.2147\/ndt.s207069","journal-title":"Neuropsychiatr Dis Treat"},{"key":"2215_CR94","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.neuron.2009.05.012","volume":"62","author":"S Li","year":"2009","unstructured":"Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D (2009) Soluble oligomers of amyloid beta protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron 62:788\u2013801. https:\/\/doi.org\/10.1016\/j.neuron.2009.05.012","journal-title":"Neuron"},{"key":"2215_CR95","doi-asserted-by":"publisher","first-page":"e0169650","DOI":"10.1371\/journal.pone.0169650","volume":"12","author":"Li Yanjun","year":"2017","unstructured":"Yanjun Li, Yongming Li, Li X, Zhang S, Zhao J, Zhu X et al (2017) Head injury as a risk factor for dementia and Alzheimer\u2019s disease: a systematic review and meta-analysis of 32 observational studies. PLoS ONE 12:e0169650. https:\/\/doi.org\/10.1371\/journal.pone.0169650","journal-title":"PLoS ONE"},{"key":"2215_CR96","doi-asserted-by":"publisher","first-page":"4023","DOI":"10.1523\/jneurosci.3442-16.2017","volume":"37","author":"C-C Liu","year":"2017","unstructured":"Liu C-C, Hu J, Zhao N, Wang J, Wang N, Cirrito JR et al (2017) Astrocytic LRP1 mediates brain A\u03b2 clearance and impacts amyloid deposition. J Neurosci 37:4023\u20134031. https:\/\/doi.org\/10.1523\/jneurosci.3442-16.2017","journal-title":"J Neurosci"},{"key":"2215_CR97","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1177\/0271678x17743670","volume":"39","author":"Q Liu","year":"2019","unstructured":"Liu Q, Radwanski R, Babadjouni R, Patel A, Hodis DM, Baumbacher P et al (2019) Experimental chronic cerebral hypoperfusion results in decreased pericyte coverage and increased blood-brain barrier permeability in the corpus callosum. J Cereb Blood Flow Metab 39:240\u2013250. https:\/\/doi.org\/10.1177\/0271678x17743670","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR98","doi-asserted-by":"publisher","first-page":"4328","DOI":"10.1007\/s12035-015-9369-x","volume":"53","author":"S-L Liu","year":"2016","unstructured":"Liu S-L, Wang C, Jiang T, Tan L, Xing A, Yu J-T (2016) The role of Cdk5 in Alzheimer\u2019s disease. Mol Neurobiol 53:4328\u20134342. https:\/\/doi.org\/10.1007\/s12035-015-9369-x","journal-title":"Mol Neurobiol"},{"key":"2215_CR99","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","volume":"179","author":"JM Long","year":"2019","unstructured":"Long JM, Holtzman DM (2019) Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179:312\u2013339. https:\/\/doi.org\/10.1016\/j.cell.2019.09.001","journal-title":"Cell"},{"key":"2215_CR100","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature14432","volume":"523","author":"A Louveau","year":"2015","unstructured":"Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD et al (2015) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337\u2013341. https:\/\/doi.org\/10.1038\/nature14432","journal-title":"Nature"},{"key":"2215_CR101","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1042\/cs20170148","volume":"131","author":"S Love","year":"2017","unstructured":"Love S, Miners JS (2017) Small vessel disease, neurovascular regulation and cognitive impairment: post-mortem studies reveal a complex relationship, still poorly understood. Clin Sci 131:1579\u20131589. https:\/\/doi.org\/10.1042\/cs20170148","journal-title":"Clin Sci"},{"key":"2215_CR102","doi-asserted-by":"publisher","first-page":"787805","DOI":"10.1155\/2015\/787805","volume":"2015","author":"MA Lovell","year":"2015","unstructured":"Lovell MA, Abner E, Kryskio R, Xu L, Fister SX, Lynn BC (2015) Calcium channel blockers, progression to dementia, and effects on amyloid beta peptide production. Oxid Med Cell Longev 2015:787805. https:\/\/doi.org\/10.1155\/2015\/787805","journal-title":"Oxid Med Cell Longev"},{"key":"2215_CR103","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1038\/s41467-017-01484-6","volume":"8","author":"Q Ma","year":"2017","unstructured":"Ma Q, Ineichen BV, Detmar M, Proulx ST (2017) Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice. Nat Commun 8:1434. https:\/\/doi.org\/10.1038\/s41467-017-01484-6","journal-title":"Nat Commun"},{"key":"2215_CR104","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.neuron.2017.12.002","volume":"97","author":"C Madry","year":"2018","unstructured":"Madry C, Kyrargyri V, Arancibia-C\u00e1rcamo IL, Jolivet R, Kohsaka S, Bryan RM et al (2018) Microglial ramification, surveillance, and interleukin-1\u03b2 release are regulated by the two-pore domain K+ channel THIK-1. Neuron 97:299\u2013312. https:\/\/doi.org\/10.1016\/j.neuron.2017.12.002","journal-title":"Neuron"},{"key":"2215_CR105","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1093\/brain\/124.6.1208","volume":"124","author":"RS Marshall","year":"2001","unstructured":"Marshall RS, Lazar RM, Pile-Spellman J, Young WL, Duong DH, Joshi S et al (2001) Recovery of brain function during induced cerebral hypoperfusion. Brain 124:1208\u20131217. https:\/\/doi.org\/10.1093\/brain\/124.6.1208","journal-title":"Brain"},{"key":"2215_CR106","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1002\/glia.21220","volume":"59","author":"T Masuda","year":"2011","unstructured":"Masuda T, Croom D, Hida H, Kirov SA (2011) Capillary blood flow around microglial somata determines dynamics of microglial processes in ischemic conditions. Glia 59:1744\u20131753. https:\/\/doi.org\/10.1002\/glia.21220","journal-title":"Glia"},{"key":"2215_CR107","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1093\/brain\/awu043","volume":"137","author":"N Mattsson","year":"2014","unstructured":"Mattsson N, Tosun D, Insel PS, Simonson A, Jack CR, Beckett LA et al (2014) Association of brain amyloid-\u03b2 with cerebral perfusion and structure in Alzheimer\u2019s disease and mild cognitive impairment. Brain 137:1550\u20131561. https:\/\/doi.org\/10.1093\/brain\/awu043","journal-title":"Brain"},{"key":"2215_CR108","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1126\/science.1197623","volume":"330","author":"KG Mawuenyega","year":"2010","unstructured":"Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC et al (2010) Decreased clearance of CNS beta-amyloid in Alzheimer\u2019s disease. Science 330:1774. https:\/\/doi.org\/10.1126\/science.1197623","journal-title":"Science"},{"key":"2215_CR109","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1080\/13543784.2017.1323868","volume":"26","author":"D Mehta","year":"2017","unstructured":"Mehta D, Jackson R, Paul G, Shi J, Sabbagh M (2017) Why do trials for Alzheimer\u2019s disease drugs keep failing? A discontinued drug perspective for 2010\u20132015. Expert Opin Investig Drugs 26:735\u2013739. https:\/\/doi.org\/10.1080\/13543784.2017.1323868","journal-title":"Expert Opin Investig Drugs"},{"key":"2215_CR110","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1016\/0735-1097(88)90297-5","volume":"11","author":"JL Mehta","year":"1988","unstructured":"Mehta JL, Nichols WW, Mehta P (1988) Neutrophils as potential participants in acute myocardial ischemia: relevance to reperfusion. J Am Coll Cardiol 11:1309\u20131316. https:\/\/doi.org\/10.1016\/0735-1097(88)90297-5","journal-title":"J Am Coll Cardiol"},{"key":"2215_CR111","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1177\/0271678x15605847","volume":"36","author":"L Michels","year":"2016","unstructured":"Michels L, Warnock G, Buck A, Macauda G, Leh SE, Kaelin AM et al (2016) Arterial spin labeling imaging reveals widespread and A\u03b2-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers. J Cereb Blood Flow Metab 36:581\u2013595. https:\/\/doi.org\/10.1177\/0271678x15605847","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR112","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1159\/000106692","volume":"5","author":"R Mielke","year":"1994","unstructured":"Mielke R, Herholz K, Grond M, Kessler J, Heiss WD (1994) Clinical deterioration in probable Alzheimer\u2019s disease correlates with progressive metabolic impairment of association areas. Dementia 5:36\u201341. https:\/\/doi.org\/10.1159\/000106692","journal-title":"Dementia"},{"key":"2215_CR113","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1016\/0278-5846(95)00031-p","volume":"19","author":"M Minami","year":"1995","unstructured":"Minami M, Kimura M, Iwamoto N, Arai H (1995) Endothelin-1-like immunoreactivity in cerebral cortex of Alzheimer-type dementia. Prog Neuropsychopharmacol Biol Psychiatry 19:509\u2013513. https:\/\/doi.org\/10.1016\/0278-5846(95)00031-p","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2215_CR114","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1111\/bpa.12331","volume":"26","author":"JS Miners","year":"2016","unstructured":"Miners JS, Palmer JC, Love S (2016) Pathophysiology of hypoperfusion of the precuneus in early Alzheimer\u2019s disease. Brain Pathol 26:533\u2013541. https:\/\/doi.org\/10.1111\/bpa.12331","journal-title":"Brain Pathol"},{"key":"2215_CR115","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1002\/ana.410420114","volume":"42","author":"S Minoshima","year":"1997","unstructured":"Minoshima S, Giordani B, Berent S, Frey KA, Foster NL, Kuhl DE (1997) Metabolic reduction in the posterior cingulate cortex in very early Alzheimer\u2019s disease. Ann Neurol 42:85\u201394. https:\/\/doi.org\/10.1002\/ana.410420114","journal-title":"Ann Neurol"},{"key":"2215_CR116","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s00401-010-0657-2","volume":"119","author":"S Mitew","year":"2010","unstructured":"Mitew S, Kirkcaldie MTK, Halliday GM, Shepherd CE, Vickers JC, Dickson TC (2010) Focal demyelination in Alzheimer\u2019s disease and transgenic mouse models. Acta Neuropathol 119:567\u2013577. https:\/\/doi.org\/10.1007\/s00401-010-0657-2","journal-title":"Acta Neuropathol"},{"key":"2215_CR117","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/nrneurol.2017.16","volume":"13","author":"VCT Mok","year":"2017","unstructured":"Mok VCT, Lam BYK, Wong A, Ko H, Markus HS, Wong LKS (2017) Early-onset and delayed-onset poststroke dementia\u2014revisiting the mechanisms. Nat Rev Neurol 13:148\u2013159. https:\/\/doi.org\/10.1038\/nrneurol.2017.16","journal-title":"Nat Rev Neurol"},{"key":"2215_CR118","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.neuron.2014.12.032","volume":"85","author":"A Montagne","year":"2015","unstructured":"Montagne A, Barnes SR, Sweeney MD, Halliday MR, Sagare AP, Zhao Z et al (2015) Blood-brain barrier breakdown in the aging human hippocampus. Neuron 85:296\u2013302. https:\/\/doi.org\/10.1016\/j.neuron.2014.12.032","journal-title":"Neuron"},{"key":"2215_CR119","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41586-020-2247-3","volume":"581","author":"A Montagne","year":"2020","unstructured":"Montagne A, Nation DA, Sagare AP, Barisano G, Sweeney MD, Chakhoyan A et al (2020) APOE4 leads to blood\u2013brain barrier dysfunction predicting cognitive decline. Nature 581:71\u201376. https:\/\/doi.org\/10.1038\/s41586-020-2247-3","journal-title":"Nature"},{"key":"2215_CR120","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s41467-017-00037-1","volume":"8","author":"YM Morizawa","year":"2017","unstructured":"Morizawa YM, Hirayama Y, Ohno N, Shibata S, Shigetomi E, Sui Y et al (2017) Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway. Nat Commun 8:28. https:\/\/doi.org\/10.1038\/s41467-017-00037-1","journal-title":"Nat Commun"},{"key":"2215_CR121","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1742-2094-10-4","volume":"10","author":"HW Morrison","year":"2013","unstructured":"Morrison HW, Filosa JA (2013) A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. J Neuroinflammation 10:4. https:\/\/doi.org\/10.1186\/1742-2094-10-4","journal-title":"J Neuroinflammation"},{"key":"2215_CR122","doi-asserted-by":"publisher","first-page":"31277","DOI":"10.1074\/jbc.M300763200","volume":"278","author":"D Mottet","year":"2003","unstructured":"Mottet D, Dumont V, Deccache Y, Demazy C, Ninane N, Raes M et al (2003) Regulation of hypoxia-inducible factor-1alpha protein level during hypoxic conditions by the phosphatidylinositol 3-kinase\/Akt\/glycogen synthase kinase 3beta pathway in HepG2 cells. J Biol Chem 278:31277\u201331285. https:\/\/doi.org\/10.1074\/jbc.M300763200","journal-title":"J Biol Chem"},{"key":"2215_CR123","doi-asserted-by":"publisher","first-page":"4050","DOI":"10.1523\/jneurosci.20-11-04050.2000","volume":"20","author":"L Mucke","year":"2000","unstructured":"Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G et al (2000) High-level neuronal expression of abeta 1\u201342 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20:4050\u20134058. https:\/\/doi.org\/10.1523\/jneurosci.20-11-04050.2000","journal-title":"J Neurosci"},{"key":"2215_CR124","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1002\/ana.23554","volume":"71","author":"M Muller","year":"2012","unstructured":"Muller M, van der Graaf Y, Visseren FL, Mali WP, Geerlings MI, SMART Study Group (2012) Hypertension and longitudinal changes in cerebral blood flow: the SMART-MR study. Ann Neurol 71:825\u2013833. https:\/\/doi.org\/10.1002\/ana.23554","journal-title":"Ann Neurol"},{"key":"2215_CR125","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1161\/strokeaha.114.006613","volume":"45","author":"KN Murray","year":"2014","unstructured":"Murray KN, Girard S, Holmes WM, Parkes LM, Williams SR, Parry-Jones AR et al (2014) Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia. Stroke 45:3412\u20133419. https:\/\/doi.org\/10.1161\/strokeaha.114.006613","journal-title":"Stroke"},{"key":"2215_CR126","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","volume":"25","author":"DA Nation","year":"2019","unstructured":"Nation DA, Sweeney MD, Montagne A, Sagare AP, D\u2019Orazio LM, Pachicano M et al (2019) Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat Med 25:270\u2013276. https:\/\/doi.org\/10.1038\/s41591-018-0297-y","journal-title":"Nat Med"},{"key":"2215_CR127","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3389\/fnagi.2020.00108","volume":"12","author":"AR Nelson","year":"2020","unstructured":"Nelson AR, Sagare MA, Wang Y, Kisler K, Zhao Z, Zlokovic BV (2020) Channelrhodopsin excitation contracts brain pericytes and reduces blood flow in the aging mouse brain in vivo. Front Aging Neurosci 12:108. https:\/\/doi.org\/10.3389\/fnagi.2020.00108","journal-title":"Front Aging Neurosci"},{"key":"2215_CR128","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1016\/j.jalz.2017.02.007","volume":"13","author":"RB Nielsen","year":"2017","unstructured":"Nielsen RB, Egefjord L, Angleys H, Mouridsen K, Gejl M, M\u00f8ller A et al (2017) Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer\u2019s disease. Alzheimers Dement 13:1143\u20131153. https:\/\/doi.org\/10.1016\/j.jalz.2017.02.007","journal-title":"Alzheimers Dement"},{"key":"2215_CR129","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1006\/nbdi.2001.0460","volume":"9","author":"K Niwa","year":"2002","unstructured":"Niwa K, Kazama K, Younkin SG, Carlson GA, Iadecola C (2002) Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein. Neurobiol Dis 9:61\u201368. https:\/\/doi.org\/10.1006\/nbdi.2001.0460","journal-title":"Neurobiol Dis"},{"key":"2215_CR130","doi-asserted-by":"publisher","first-page":"H2417","DOI":"10.1152\/ajpheart.2001.281.6.H2417","volume":"281","author":"K Niwa","year":"2001","unstructured":"Niwa K, Porter VA, Kazama K, Cornfield D, Carlson GA, Iadecola C (2001) A beta-peptides enhance vasoconstriction in cerebral circulation. Am J Physiol Heart Circ Physiol 281:H2417\u20132424. https:\/\/doi.org\/10.1152\/ajpheart.2001.281.6.H2417","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2215_CR131","doi-asserted-by":"publisher","first-page":"9735","DOI":"10.1073\/pnas.97.17.9735","volume":"97","author":"K Niwa","year":"2000","unstructured":"Niwa K, Younkin L, Ebeling C, Turner SK, Westaway D, Younkin S et al (2000) Abeta 1\u201340-related reduction in functional hyperemia in mouse neocortex during somatosensory activation. Proc Natl Acad Sci USA 97:9735\u20139740. https:\/\/doi.org\/10.1073\/pnas.97.17.9735","journal-title":"Proc Natl Acad Sci USA"},{"key":"2215_CR132","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1182\/blood-2001-12-0190","volume":"101","author":"KE Norman","year":"2003","unstructured":"Norman KE, Cotter MJ, Stewart JB, Abbitt KB, Ali M, Wagner BE et al (2003) Combined anticoagulant and antiselectin treatments prevent lethal intravascular coagulation. Blood 101:921\u2013928. https:\/\/doi.org\/10.1182\/blood-2001-12-0190","journal-title":"Blood"},{"key":"2215_CR133","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav9518","author":"R Nortley","year":"2019","unstructured":"Nortley R, Korte N, Izquierdo P, Hirunpattarasilp C, Mishra A, Jaunmuktane Z et al (2019) Amyloid \u03b2 oligomers constrict human capillaries in Alzheimer\u2019s disease via signaling to pericytes. Science. https:\/\/doi.org\/10.1126\/science.aav9518","journal-title":"Science"},{"key":"2215_CR134","doi-asserted-by":"publisher","first-page":"3487","DOI":"10.2147\/ndt.s225754","volume":"15","author":"M Ortner","year":"2019","unstructured":"Ortner M, Hauser C, Schmaderer C, Muggenthaler C, Hapfelmeier A, Sorg C et al (2019) Decreased vascular pulsatility in Alzheimer\u2019s disease dementia measured by transcranial color-coded duplex sonography. Neuropsychiatr Dis Treat 15:3487\u20133499. https:\/\/doi.org\/10.2147\/ndt.s225754","journal-title":"Neuropsychiatr Dis Treat"},{"key":"2215_CR135","doi-asserted-by":"publisher","first-page":"853","DOI":"10.3233\/JAD-2012-111760","volume":"29","author":"JC Palmer","year":"2012","unstructured":"Palmer JC, Barker R, Kehoe PG, Love S (2012) Endothelin-1 is elevated in Alzheimer\u2019s disease and upregulated by amyloid-\u03b2. J Alzheimers Dis 29:853\u2013861. https:\/\/doi.org\/10.3233\/JAD-2012-111760","journal-title":"J Alzheimers Dis"},{"key":"2215_CR136","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/ana.25410","volume":"85","author":"F Panza","year":"2019","unstructured":"Panza F, Lozupone M, Seripa D, Imbimbo BP (2019) Amyloid-\u03b2 immunotherapy for alzheimer disease: is it now a long shot? Ann Neurol 85:303\u2013315. https:\/\/doi.org\/10.1002\/ana.25410","journal-title":"Ann Neurol"},{"key":"2215_CR137","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.nbd.2014.07.012","volume":"71","author":"M Pappolla","year":"2014","unstructured":"Pappolla M, Sambamurti K, Vidal R, Pacheco-Quinto J, Poeggeler B, Matsubara E (2014) Evidence for lymphatic A\u03b2 clearance in Alzheimer\u2019s transgenic mice. Neurobiol Dis 71:215\u2013219. https:\/\/doi.org\/10.1016\/j.nbd.2014.07.012","journal-title":"Neurobiol Dis"},{"key":"2215_CR138","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1038\/s41593-018-0296-9","volume":"22","author":"S Parhizkar","year":"2019","unstructured":"Parhizkar S, Arzberger T, Brendel M, Kleinberger G, Deussing M, Focke C et al (2019) Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE. Nat Neurosci 22:191\u2013204. https:\/\/doi.org\/10.1038\/s41593-018-0296-9","journal-title":"Nat Neurosci"},{"key":"2215_CR139","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.brainres.2003.11.061","volume":"999","author":"D Paris","year":"2004","unstructured":"Paris D, Quadros A, Humphrey J, Patel N, Crescentini R, Crawford F et al (2004) Nilvadipine antagonizes both Abeta vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice. Brain Res 999:53\u201361. https:\/\/doi.org\/10.1016\/j.brainres.2003.11.061","journal-title":"Brain Res"},{"key":"2215_CR140","doi-asserted-by":"publisher","first-page":"14102","DOI":"10.1038\/s41598-019-50681-4","volume":"9","author":"J-H Park","year":"2019","unstructured":"Park J-H, Hong J-H, Lee S-W, Ji HD, Jung J-A, Yoon K-W et al (2019) The effect of chronic cerebral hypoperfusion on the pathology of Alzheimer\u2019s disease: a positron emission tomography study in rats. Sci Rep 9:14102. https:\/\/doi.org\/10.1038\/s41598-019-50681-4","journal-title":"Sci Rep"},{"key":"2215_CR141","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1161\/CIRCRESAHA.117.311054","volume":"121","author":"L Park","year":"2017","unstructured":"Park L, Uekawa K, Garcia-Bonilla L, Koizumi K, Murphy M, Pistik R et al (2017) Brain perivascular macrophages initiate the neurovascular dysfunction of Alzheimer A\u03b2 peptides. Circ Res 121:258\u2013269. https:\/\/doi.org\/10.1161\/CIRCRESAHA.117.311054","journal-title":"Circ Res"},{"key":"2215_CR142","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.nbd.2016.05.015","volume":"93","author":"W Peng","year":"2016","unstructured":"Peng W, Achariyar TM, Li B, Liao Y, Mestre H, Hitomi E et al (2016) Suppression of glymphatic fluid transport in a mouse model of Alzheimer\u2019s disease. Neurobiol Dis 93:215\u2013225. https:\/\/doi.org\/10.1016\/j.nbd.2016.05.015","journal-title":"Neurobiol Dis"},{"key":"2215_CR143","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1038\/nature05193","volume":"443","author":"CM Peppiatt","year":"2006","unstructured":"Peppiatt CM, Howarth C, Mobbs P, Attwell D (2006) Bidirectional control of CNS capillary diameter by pericytes. Nature 443:700\u2013704. https:\/\/doi.org\/10.1038\/nature05193","journal-title":"Nature"},{"key":"2215_CR144","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1212\/wnl.38.6.931","volume":"38","author":"I Prohovnik","year":"1988","unstructured":"Prohovnik I, Mayeux R, Sackeim HA, Smith G, Stern Y, Alderson PO (1988) Cerebral perfusion as a diagnostic marker of early Alzheimer\u2019s disease. Neurology 38:931\u2013937. https:\/\/doi.org\/10.1212\/wnl.38.6.931","journal-title":"Neurology"},{"key":"2215_CR145","doi-asserted-by":"publisher","first-page":"23964","DOI":"10.1038\/srep23964","volume":"6","author":"L Qiu","year":"2016","unstructured":"Qiu L, Ng G, Tan EK, Liao P, Kandiah N, Zeng L (2016) Chronic cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer\u2019s disease mice. Sci Rep 6:23964. https:\/\/doi.org\/10.1038\/srep23964","journal-title":"Sci Rep"},{"key":"2215_CR146","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41598-018-37271-6","volume":"9","author":"G Querques","year":"2019","unstructured":"Querques G, Borrelli E, Sacconi R, De Vitis L, Leocani L, Santangelo R et al (2019) Functional and morphological changes of the retinal vessels in Alzheimer\u2019s disease and mild cognitive impairment. Sci Rep 9:63. https:\/\/doi.org\/10.1038\/s41598-018-37271-6","journal-title":"Sci Rep"},{"key":"2215_CR147","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.nbd.2018.07.009","volume":"126","author":"L Raz","year":"2019","unstructured":"Raz L, Bhaskar K, Weaver J, Marini S, Zhang Q, Thompson JF et al (2019) Hypoxia promotes tau hyperphosphorylation with associated neuropathology in vascular dysfunction. Neurobiol Dis 126:124\u2013136. https:\/\/doi.org\/10.1016\/j.nbd.2018.07.009","journal-title":"Neurobiol Dis"},{"key":"2215_CR148","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1056\/NEJM199603213341202","volume":"334","author":"EM Reiman","year":"1996","unstructured":"Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S et al (1996) Preclinical evidence of Alzheimer\u2019s disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med 334:752\u2013758. https:\/\/doi.org\/10.1056\/NEJM199603213341202","journal-title":"N Engl J Med"},{"key":"2215_CR149","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.biopsych.2004.10.039","volume":"57","author":"M-S Roh","year":"2005","unstructured":"Roh M-S, Eom T-Y, Zmijewska AA, De Sarno P, Roth KA, Jope RS (2005) Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: protection by mood stabilizers and imipramine. Biol Psychiatry 57:278\u2013286. https:\/\/doi.org\/10.1016\/j.biopsych.2004.10.039","journal-title":"Biol Psychiatry"},{"key":"2215_CR150","doi-asserted-by":"publisher","first-page":"12447","DOI":"10.1074\/jbc.m804740200","volume":"284","author":"N Rudinskiy","year":"2009","unstructured":"Rudinskiy N, Grishchuk Y, Vaslin A, Puyal J, Delacourte A, Hirling H et al (2009) Calpain hydrolysis of alpha- and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration. J Biol Chem 284:12447\u201312458. https:\/\/doi.org\/10.1074\/jbc.m804740200","journal-title":"J Biol Chem"},{"key":"2215_CR151","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1002\/ana.20493","volume":"57","author":"A Ruitenberg","year":"2005","unstructured":"Ruitenberg A, den Heijer T, Bakker SLM, van Swieten JC, Koudstaal PJ, Hofman A et al (2005) Cerebral hypoperfusion and clinical onset of dementia: the Rotterdam Study. Ann Neurol 57:789\u2013794. https:\/\/doi.org\/10.1002\/ana.20493","journal-title":"Ann Neurol"},{"key":"2215_CR152","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.neuron.2018.06.012","volume":"99","author":"RL Rungta","year":"2018","unstructured":"Rungta RL, Chaigneau E, Osmanski B-F, Charpak S (2018) Vascular compartmentalization of functional hyperemia from the synapse to the pia. Neuron 99:362\u2013375. https:\/\/doi.org\/10.1016\/j.neuron.2018.06.012","journal-title":"Neuron"},{"key":"2215_CR153","doi-asserted-by":"publisher","first-page":"2932","DOI":"10.1038\/ncomms3932","volume":"4","author":"AP Sagare","year":"2013","unstructured":"Sagare AP, Bell RD, Zhao Z, Ma Q, Winkler EA, Ramanathan A et al (2013) Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat Commun 4:2932. https:\/\/doi.org\/10.1038\/ncomms3932","journal-title":"Nat Commun"},{"key":"2215_CR154","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1161\/strokeaha.115.010528","volume":"47","author":"R Sahathevan","year":"2016","unstructured":"Sahathevan R, Linden T, Villemagne VL, Churilov L, Ly JV, Rowe C et al (2016) Positron emission tomographic imaging in stroke: cross-sectional and follow-up assessment of amyloid in ischemic stroke. Stroke 47:113\u2013119. https:\/\/doi.org\/10.1161\/strokeaha.115.010528","journal-title":"Stroke"},{"key":"2215_CR155","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.neuron.2019.06.002","volume":"103","author":"DK Sandsmark","year":"2019","unstructured":"Sandsmark DK, Bashir A, Wellington CL, Diaz-Arrastia R (2019) Cerebral microvascular injury: a potentially treatable endophenotype of traumatic brain injury-induced neurodegeneration. Neuron 103:367\u2013379. https:\/\/doi.org\/10.1016\/j.neuron.2019.06.002","journal-title":"Neuron"},{"key":"2215_CR156","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.jtbi.2005.07.005","volume":"238","author":"D Schley","year":"2006","unstructured":"Schley D, Carare-Nnadi R, Please CP, Perry VH, Weller RO (2006) Mechanisms to explain the reverse perivascular transport of solutes out of the brain. J Theor Biol 238:962\u2013974. https:\/\/doi.org\/10.1016\/j.jtbi.2005.07.005","journal-title":"J Theor Biol"},{"key":"2215_CR157","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1126\/science.1074069","volume":"298","author":"DJ Selkoe","year":"2002","unstructured":"Selkoe DJ (2002) Alzheimer\u2019s disease is a synaptic failure. Science 298:789\u2013791. https:\/\/doi.org\/10.1126\/science.1074069","journal-title":"Science"},{"key":"2215_CR158","doi-asserted-by":"publisher","first-page":"9917","DOI":"10.1523\/JNEUROSCI.0621-17.2017","volume":"37","author":"J Seo","year":"2017","unstructured":"Seo J, Kritskiy O, Watson LA, Barker SJ, Dey D, Raja WK et al (2017) Inhibition of p25\/Cdk5 attenuates tauopathy in mouse and iPSC models of frontotemporal dementia. J Neurosci 37:9917\u20139924. https:\/\/doi.org\/10.1523\/JNEUROSCI.0621-17.2017","journal-title":"J Neurosci"},{"key":"2215_CR159","doi-asserted-by":"publisher","DOI":"10.1177\/0271678x19895245","author":"B Shager","year":"2020","unstructured":"Shager B, Brown CE (2020) Susceptibility to capillary plugging can predict brain region specific vessel loss with aging. J Cereb Blood Flow Metab. https:\/\/doi.org\/10.1177\/0271678x19895245. (Epub ahead of print)","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR160","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1172\/jci10498","volume":"106","author":"M Shibata","year":"2000","unstructured":"Shibata M, Yamada S, Kumar SR, Calero M, Bading J, Frangione B et al (2000) Clearance of Alzheimer\u2019s amyloid-ss(1\u201340) peptide from brain by LDL receptor-related protein-1 at the blood-brain barrier. J Clin Invest 106:1489\u20131499. https:\/\/doi.org\/10.1172\/jci10498","journal-title":"J Clin Invest"},{"key":"2215_CR161","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1194\/jlr.r075796","volume":"58","author":"M Shinohara","year":"2017","unstructured":"Shinohara M, Tachibana M, Kanekiyo T, Bu G (2017) Role of LRP1 in the pathogenesis of Alzheimer\u2019s disease: evidence from clinical and preclinical studies. J Lipid Res 58:1267\u20131281. https:\/\/doi.org\/10.1194\/jlr.r075796","journal-title":"J Lipid Res"},{"key":"2215_CR162","doi-asserted-by":"publisher","first-page":"6037","DOI":"10.1073\/pnas.090106797","volume":"97","author":"GW Small","year":"2000","unstructured":"Small GW, Ercoli LM, Silverman DH, Huang SC, Komo S, Bookheimer SY et al (2000) Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer\u2019s disease. Proc Natl Acad Sci USA 97:6037\u20136042. https:\/\/doi.org\/10.1073\/pnas.090106797","journal-title":"Proc Natl Acad Sci USA"},{"key":"2215_CR163","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1001\/jama.1995.03520360056039","volume":"273","author":"GW Small","year":"1995","unstructured":"Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA et al (1995) Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 273:942\u2013947. https:\/\/doi.org\/10.1001\/jama.1995.03520360056039","journal-title":"JAMA"},{"key":"2215_CR164","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1096\/fj.201700999","volume":"32","author":"AJ Smith","year":"2018","unstructured":"Smith AJ, Verkman AS (2018) The \u201cglymphatic\u201d mechanism for solute clearance in Alzheimer\u2019s disease: game changer or unproven speculation? FASEB J 32:543\u2013551. https:\/\/doi.org\/10.1096\/fj.201700999","journal-title":"FASEB J"},{"key":"2215_CR165","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1001\/archneur.1992.00530350056020","volume":"49","author":"GS Smith","year":"1992","unstructured":"Smith GS, de Leon MJ, George AE, Kluger A, Volkow ND, McRae T et al (1992) Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer\u2019s disease. Pathophysiologic implications. Arch Neurol 49:1142\u20131150. https:\/\/doi.org\/10.1001\/archneur.1992.00530350056020","journal-title":"Arch Neurol"},{"key":"2215_CR166","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1161\/circulationaha.117.033383","volume":"138","author":"K \u0160piranec","year":"2018","unstructured":"\u0160piranec K, Chen W, Werner F, Nikolaev VO, Naruke T, Koch F et al (2018) Endothelial C-type natriuretic peptide acts on pericytes to regulate microcirculatory flow and blood pressure. Circulation 138:494\u2013508. https:\/\/doi.org\/10.1161\/circulationaha.117.033383","journal-title":"Circulation"},{"key":"2215_CR167","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1172\/jci81108","volume":"126","author":"SE Storck","year":"2016","unstructured":"Storck SE, Meister S, Nahrath J, Mei\u00dfner JN, Schubert N, Spiezio A et al (2016) Endothelial LRP1 transports amyloid-\u03b2(1\u201342) across the blood-brain barrier. J Clin Invest 126:123\u2013136. https:\/\/doi.org\/10.1172\/jci81108","journal-title":"J Clin Invest"},{"key":"2215_CR168","doi-asserted-by":"publisher","first-page":"18727","DOI":"10.1073\/pnas.0606298103","volume":"103","author":"X Sun","year":"2006","unstructured":"Sun X, He G, Qing H, Zhou W, Dobie F, Cai F et al (2006) Hypoxia facilitates Alzheimer\u2019s disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci USA 103:18727\u201318732. https:\/\/doi.org\/10.1073\/pnas.0606298103","journal-title":"Proc Natl Acad Sci USA"},{"key":"2215_CR169","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/s0304-3940(98)00814-3","volume":"257","author":"Z Suo","year":"1998","unstructured":"Suo Z, Humphrey J, Kundtz A, Sethi F, Placzek A, Crawford F et al (1998) Soluble Alzheimer\u2019s beta-amyloid constricts the cerebral vasculature in vivo. Neurosci Lett 257:77\u201380. https:\/\/doi.org\/10.1016\/s0304-3940(98)00814-3","journal-title":"Neurosci Lett"},{"key":"2215_CR170","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.jns.2009.09.033","volume":"288","author":"R Takahashi","year":"2010","unstructured":"Takahashi R, Ishii K, Shimada K, Ohkawa S, Nishimura Y (2010) Hypoperfusion of the motor cortex associated with parkinsonism in dementia with Lewy bodies. J Neurol Sci 288:88\u201391. https:\/\/doi.org\/10.1016\/j.jns.2009.09.033","journal-title":"J Neurol Sci"},{"key":"2215_CR171","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.neuron.2007.05.012","volume":"54","author":"G Tesco","year":"2007","unstructured":"Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M et al (2007) Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. Neuron 54:721\u2013737. https:\/\/doi.org\/10.1016\/j.neuron.2007.05.012","journal-title":"Neuron"},{"key":"2215_CR172","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1001\/archneurol.2009.913","volume":"67","author":"M Thambisetty","year":"2010","unstructured":"Thambisetty M, Beason-Held L, An Y, Kraut MA, Resnick SM (2010) APOE epsilon4 genotype and longitudinal changes in cerebral blood flow in normal aging. Arch Neurol 67:93\u201398. https:\/\/doi.org\/10.1001\/archneurol.2009.913","journal-title":"Arch Neurol"},{"key":"2215_CR173","doi-asserted-by":"publisher","first-page":"637","DOI":"10.3389\/fnins.2019.00637","volume":"13","author":"AM Thiebault","year":"2019","unstructured":"Thiebault AM, Hedou E, Marciniak SJ, Vivien D, Roussel BD (2019) Proteostasis during cerebral ischemia. Front Neurosci 13:637. https:\/\/doi.org\/10.3389\/fnins.2019.00637","journal-title":"Front Neurosci"},{"key":"2215_CR174","doi-asserted-by":"publisher","first-page":"4705","DOI":"10.1523\/JNEUROSCI.0169-12.2012","volume":"32","author":"X-K Tong","year":"2012","unstructured":"Tong X-K, Lecrux C, Rosa-Neto P, Hamel E (2012) Age-dependent rescue by simvastatin of Alzheimer\u2019s disease cerebrovascular and memory deficits. J Neurosci 32:4705\u20134715. https:\/\/doi.org\/10.1523\/JNEUROSCI.0169-12.2012","journal-title":"J Neurosci"},{"key":"2215_CR175","doi-asserted-by":"publisher","first-page":"797","DOI":"10.2165\/00044011-200727110-00006","volume":"27","author":"PLM van Giersbergen","year":"2007","unstructured":"van Giersbergen PLM, Dingemanse J (2007) Effect of gender on the tolerability, safety and pharmacokinetics of clazosentan following long-term infusion. Clin Drug Investig 27:797\u2013802. https:\/\/doi.org\/10.2165\/00044011-200727110-00006","journal-title":"Clin Drug Investig"},{"key":"2215_CR176","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/j.cell.2012.02.046","volume":"149","author":"L Verret","year":"2012","unstructured":"Verret L, Mann EO, Hang GB, Barth AMI, Cobos I, Ho K et al (2012) Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model. Cell 149:708\u2013721. https:\/\/doi.org\/10.1016\/j.cell.2012.02.046","journal-title":"Cell"},{"key":"2215_CR177","doi-asserted-by":"publisher","first-page":"813","DOI":"10.3233\/JAD-2010-100216","volume":"21","author":"X Wang","year":"2010","unstructured":"Wang X, Xing A, Xu C, Cai Q, Liu H, Li L (2010) Cerebrovascular hypoperfusion induces spatial memory impairment, synaptic changes, and amyloid-\u03b2 oligomerization in rats. J Alzheimers Dis 21:813\u2013822. https:\/\/doi.org\/10.3233\/JAD-2010-100216","journal-title":"J Alzheimers Dis"},{"key":"2215_CR178","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1089\/neu.2015.4072","volume":"33","author":"Y Wang","year":"2016","unstructured":"Wang Y, Nelson LD, LaRoche AA, Pfaller AY, Nencka AS, Koch KM et al (2016) Cerebral blood flow alterations in acute sport-related concussion. J Neurotrauma 33:1227\u20131236. https:\/\/doi.org\/10.1089\/neu.2015.4072","journal-title":"J Neurotrauma"},{"key":"2215_CR179","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1111\/j.1750-3639.2008.00133.x","volume":"18","author":"RO Weller","year":"2008","unstructured":"Weller RO, Subash M, Preston SD, Mazanti I, Carare RO (2008) Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Brain Pathol 18:253\u2013266. https:\/\/doi.org\/10.1111\/j.1750-3639.2008.00133.x","journal-title":"Brain Pathol"},{"issue":"Suppl 4","key":"2215_CR180","doi-asserted-by":"publisher","first-page":"S411","DOI":"10.3233\/JAD-141467","volume":"42","author":"CE Wierenga","year":"2014","unstructured":"Wierenga CE, Hays CC, Zlatar ZZ (2014) Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer\u2019s disease. J Alzheimers Dis 42(Suppl 4):S411\u2013419. https:\/\/doi.org\/10.3233\/JAD-141467","journal-title":"J Alzheimers Dis"},{"key":"2215_CR181","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.2353\/ajpath.2007.070050","volume":"171","author":"MM Wilhelmus","year":"2007","unstructured":"Wilhelmus MM, Otte-H\u00f6ller I, van Triel JJ, Veerhuis R, Maat-Schieman ML, Bu G et al (2007) Lipoprotein receptor-related protein-1 mediates amyloid-beta-mediated cell death of cerebrovascular cells. Am J Pathol 171:1989\u20131999. https:\/\/doi.org\/10.2353\/ajpath.2007.070050","journal-title":"Am J Pathol"},{"key":"2215_CR182","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41593-020-0635-5","volume":"23","author":"AP Wingo","year":"2020","unstructured":"Wingo AP, Fan W, Duong DM, Gerasimov ES, Dammer EB, Liu Y et al (2020) Shared proteomic effects of cerebral atherosclerosis and Alzheimer\u2019s disease on the human brain. Nat Neurosci 23:696\u2013700. https:\/\/doi.org\/10.1038\/s41593-020-0635-5","journal-title":"Nat Neurosci"},{"key":"2215_CR183","doi-asserted-by":"publisher","first-page":"e4593","DOI":"10.1097\/md.0000000000004593","volume":"95","author":"C-L Wu","year":"2016","unstructured":"Wu C-L, Wen S-H (2016) A 10-year follow-up study of the association between calcium channel blocker use and the risk of dementia in elderly hypertensive patients. Medicine 95:e4593. https:\/\/doi.org\/10.1097\/md.0000000000004593","journal-title":"Medicine"},{"key":"2215_CR184","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.nbd.2008.08.007","volume":"32","author":"M Xiong","year":"2008","unstructured":"Xiong M, Zhang T, Zhang L-M, Lu S-D, Huang Y-L, Sun F-Y (2008) Caspase inhibition attenuates accumulation of beta-amyloid by reducing beta-secretase production and activity in rat brains after stroke. Neurobiol Dis 32:433\u2013441. https:\/\/doi.org\/10.1016\/j.nbd.2008.08.007","journal-title":"Neurobiol Dis"},{"key":"2215_CR185","doi-asserted-by":"publisher","first-page":"11782","DOI":"10.1038\/s41598-019-48279-x","volume":"9","author":"M Yamada","year":"2019","unstructured":"Yamada M, Hayashi H, Suzuki K, Sato S, Inoue D, Iwatani Y et al (2019) Furin-mediated cleavage of LRP1 and increase in ICD of LRP1 after cerebral ischemia and after exposure of cultured neurons to NMDA. Sci Rep 9:11782. https:\/\/doi.org\/10.1038\/s41598-019-48279-x","journal-title":"Sci Rep"},{"key":"2215_CR186","doi-asserted-by":"publisher","first-page":"711","DOI":"10.3233\/jad-2011-110725","volume":"27","author":"J Yang","year":"2011","unstructured":"Yang J, Lunde LK, Nuntagij P, Oguchi T, Camassa LMA, Nilsson LNG et al (2011) Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer\u2019s disease. J Alzheimers Dis 27:711\u2013722. https:\/\/doi.org\/10.3233\/jad-2011-110725","journal-title":"J Alzheimers Dis"},{"key":"2215_CR187","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1038\/nm.2022","volume":"15","author":"M Yemisci","year":"2009","unstructured":"Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T (2009) Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med 15:1031\u20131037. https:\/\/doi.org\/10.1038\/nm.2022","journal-title":"Nat Med"},{"key":"2215_CR188","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1093\/brain\/awx112","volume":"140","author":"B Yew","year":"2017","unstructured":"Yew B, Nation DA, Alzheimer\u2019s Disease Neuroimaging Initiative (2017) Cerebrovascular resistance: effects on cognitive decline, cortical atrophy, and progression to dementia. Brain 140:1987\u20132001. https:\/\/doi.org\/10.1093\/brain\/awx112","journal-title":"Brain"},{"key":"2215_CR189","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3233\/JAD-161047","volume":"59","author":"C-H Yun","year":"2017","unstructured":"Yun C-H, Lee H-Y, Lee SK, Kim H, Seo HS, Bang SA et al (2017) Amyloid burden in obstructive sleep apnea. J Alzheimers Dis 59:21\u201329. https:\/\/doi.org\/10.3233\/JAD-161047","journal-title":"J Alzheimers Dis"},{"key":"2215_CR190","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.cell.2018.06.021","volume":"174","author":"A Zeisel","year":"2018","unstructured":"Zeisel A, Hochgerner H, L\u00f6nnerberg P, Johnsson A, Memic F, van der Zwan J et al (2018) Molecular architecture of the mouse nervous system. Cell 174:999\u20131014. https:\/\/doi.org\/10.1016\/j.cell.2018.06.021","journal-title":"Cell"},{"key":"2215_CR191","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1161\/CIRCRESAHA.111.249532","volume":"109","author":"P Zhai","year":"2011","unstructured":"Zhai P, Sciarretta S, Galeotti J, Volpe M, Sadoshima J (2011) Differential roles of GSK-3\u03b2 during myocardial ischemia and ischemia\/reperfusion. Circ Res 109:502\u2013511. https:\/\/doi.org\/10.1161\/CIRCRESAHA.111.249532","journal-title":"Circ Res"},{"key":"2215_CR192","doi-asserted-by":"publisher","first-page":"249","DOI":"10.14336\/ad.2017.0424","volume":"9","author":"C Zhang","year":"2018","unstructured":"Zhang C, Zhu Y, Wang S, Zachory WZ, Jiang MQ, Zhang Y et al (2018) Temporal gene expression profiles after focal cerebral ischemia in mice. Aging Dis 9:249\u2013261. https:\/\/doi.org\/10.14336\/ad.2017.0424","journal-title":"Aging Dis"},{"key":"2215_CR193","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1093\/nsr\/nwz124","volume":"6","author":"X Zhang","year":"2019","unstructured":"Zhang X, Yin X, Zhang J, Li A, Gong H, Luo Q et al (2019) High resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer\u2019s disease mice. Natl Sci Rev 6:1223\u20131238. https:\/\/doi.org\/10.1093\/nsr\/nwz124","journal-title":"Natl Sci Rev"},{"key":"2215_CR194","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/jcbfm.2009.228","volume":"30","author":"Y Zhang","year":"2010","unstructured":"Zhang Y, Xiong M, Yan R-Q, Sun F-Y (2010) Mutant ubiquitin-mediated beta-secretase stability via activation of caspase-3 is related to beta-amyloid accumulation in ischemic striatum in rats. J Cereb Blood Flow Metab 30:566\u2013575. https:\/\/doi.org\/10.1038\/jcbfm.2009.228","journal-title":"J Cereb Blood Flow Metab"},{"key":"2215_CR195","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.neuron.2018.01.031","volume":"97","author":"Y Zhao","year":"2018","unstructured":"Zhao Y, Wu X, Li X, Jiang L-L, Gui X, Liu Y et al (2018) TREM2 Is a receptor for \u03b2-amyloid that mediates microglial function. Neuron 97:1023\u20131031. https:\/\/doi.org\/10.1016\/j.neuron.2018.01.031","journal-title":"Neuron"},{"key":"2215_CR196","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1038\/nn.4025","volume":"18","author":"Z Zhao","year":"2015","unstructured":"Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K et al (2015) Central role for PICALM in amyloid-\u03b2 blood-brain barrier transcytosis and clearance. Nat Neurosci 18:978\u2013987. https:\/\/doi.org\/10.1038\/nn.4025","journal-title":"Nat Neurosci"},{"key":"2215_CR197","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1007\/s11064-008-9899-y","volume":"34","author":"C Zhiyou","year":"2009","unstructured":"Zhiyou C, Yong Y, Shanquan S, Jun Z, Liangguo H, Ling Y et al (2009) Upregulation of BACE1 and beta-amyloid protein mediated by chronic cerebral hypoperfusion contributes to cognitive impairment and pathogenesis of Alzheimer\u2019s disease. Neurochem Res 34:1226\u20131235. https:\/\/doi.org\/10.1007\/s11064-008-9899-y","journal-title":"Neurochem Res"},{"key":"2215_CR198","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.tins.2005.02.001","volume":"28","author":"BV Zlokovic","year":"2005","unstructured":"Zlokovic BV (2005) Neurovascular mechanisms of Alzheimer\u2019s neurodegeneration. Trends Neurosci 28:202\u2013208. https:\/\/doi.org\/10.1016\/j.tins.2005.02.001","journal-title":"Trends Neurosci"},{"key":"2215_CR199","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1126\/science.aay0198","volume":"365","author":"B Zott","year":"2019","unstructured":"Zott B, Simon MM, Hong W, Unger F, Chen-Engerer H-J, Frosch MP, Sakmann B et al (2019) A vicious cycle of \u03b2 amyloid-dependent neuronal hyperactivation. Science 365:559\u2013565. https:\/\/doi.org\/10.1126\/science.aay0198","journal-title":"Science"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-020-02215-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-020-02215-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-020-02215-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T23:24:58Z","timestamp":1630365898000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-020-02215-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,31]]},"references-count":199,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2215"],"URL":"https:\/\/doi.org\/10.1007\/s00401-020-02215-w","relation":{},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,31]]},"assertion":[{"value":"23 June 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}