{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:34:48Z","timestamp":1792892088740,"version":"4.5.0"},"reference-count":102,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG054023"],"award-info":[{"award-number":["RF1AG054023"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG067501"],"award-info":[{"award-number":["R01 AG067501"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG072474"],"award-info":[{"award-number":["R01 AG072474"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56AG051876"],"award-info":[{"award-number":["R56AG051876"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30AG10161"],"award-info":[{"award-number":["P30AG10161"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG15819"],"award-info":[{"award-number":["R01AG15819"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG17917"],"award-info":[{"award-number":["R01AG17917"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG61356"],"award-info":[{"award-number":["U01AG61356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG036836"],"award-info":[{"award-number":["R01AG036836"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AG046152"],"award-info":[{"award-number":["U01AG046152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001656","name":"Helmholtz-Gemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001656","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer\u2019s disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified\n                    <jats:italic>FMNL2<\/jats:italic>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20096.6\u2009\u00d7\u200910\n                    <jats:sup>\u20137<\/jats:sup>\n                    ). A significant increase in\n                    <jats:italic>FMNL2<\/jats:italic>\n                    expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased\n                    <jats:italic>fmnl2a<\/jats:italic>\n                    expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of\n                    <jats:italic>fmnl2a<\/jats:italic>\n                    prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP\/PS1dE9 AD mice also displayed increased\n                    <jats:italic>Fmnl2<\/jats:italic>\n                    expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood\u2013brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with\n                    <jats:italic>FMNL2<\/jats:italic>\n                    altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.\n                  <\/jats:p>","DOI":"10.1007\/s00401-022-02431-6","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T03:02:52Z","timestamp":1653361372000},"page":"59-79","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer\u2019s disease"],"prefix":"10.1007","volume":"144","author":[{"given":"Annie J.","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha S.","family":"Raghavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabesh","family":"Bhattarai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohid","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Sariya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolly","family":"Reyes-Dumeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xena E.","family":"Flowers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah A. L.","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip L.","family":"De Jager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilas","family":"Menon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael A.","family":"Lantigua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Medrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diones","family":"Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne Z.","family":"Jim\u00e9nez-Vel\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter A.","family":"Kukull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Brickman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer J.","family":"Manly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tosto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caghan","family":"Kizil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Badri N.","family":"Vardarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mayeux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"2431_CR1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677219869037","author":"P Alestrom","year":"2019","unstructured":"Alestrom P, D\u2019Angelo L, Midtlyng PJ, Schorderet DF, Schulte-Merker S, Sohm F et al (2019) Zebrafish: housing and husbandry recommendations. Lab Anim. https:\/\/doi.org\/10.1177\/0023677219869037","journal-title":"Lab Anim"},{"key":"2431_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2016.89","volume":"3","author":"M Allen","year":"2016","unstructured":"Allen M, Carrasquillo MM, Funk C, Heavner BD, Zou F, Younkin CS et al (2016) Human whole genome genotype and transcriptome data for Alzheimer\u2019s and other neurodegenerative diseases. Sci Data 3:160089. https:\/\/doi.org\/10.1038\/sdata.2016.89","journal-title":"Sci Data"},{"key":"2431_CR3","doi-asserted-by":"publisher","unstructured":"Anael Cain MT, McCabe C, Hekselman I, White CC, Green G, Rozenblatt-Rosen O et al (2020) Multi-cellular communities are perturbed in the aging human brain and with Alzheimer\u2019s disease. bioRxiv. https:\/\/doi.org\/10.1101\/2020.12.22.424084","DOI":"10.1101\/2020.12.22.424084"},{"key":"2431_CR4","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12916-014-0206-2","volume":"12","author":"J Attems","year":"2014","unstructured":"Attems J, Jellinger KA (2014) The overlap between vascular disease and Alzheimer\u2019s disease\u2013lessons from pathology. BMC Med 12:206. https:\/\/doi.org\/10.1186\/s12916-014-0206-2","journal-title":"BMC Med"},{"key":"2431_CR5","doi-asserted-by":"publisher","first-page":"H740","DOI":"10.1152\/ajpheart.00736.2020","volume":"320","author":"P Balasubramanian","year":"2021","unstructured":"Balasubramanian P, Kiss T, Tarantini S, Nyul-Toth A, Ahire C, Yabluchanskiy A et al (2021) Obesity-induced cognitive impairment in older adults: a microvascular perspective. Am J Physiol Heart Circ Physiol 320:H740\u2013H761. https:\/\/doi.org\/10.1152\/ajpheart.00736.2020","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2431_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01024-z","author":"C Bellenguez","year":"2022","unstructured":"Bellenguez C, Kucukali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N et al (2022) New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias. Nat Genet. https:\/\/doi.org\/10.1038\/s41588-022-01024-z","journal-title":"Nat Genet"},{"key":"2431_CR7","doi-asserted-by":"publisher","first-page":"S161","DOI":"10.3233\/JAD-179939","volume":"64","author":"DA Bennett","year":"2018","unstructured":"Bennett DA, Buchman AS, Boyle PA, Barnes LL, Wilson RS, Schneider JA (2018) Religious orders study and rush memory and aging project. J Alzheimers Dis 64:S161\u2013S189. https:\/\/doi.org\/10.3233\/JAD-179939","journal-title":"J Alzheimers Dis"},{"key":"2431_CR8","doi-asserted-by":"publisher","first-page":"628","DOI":"10.2174\/156720512801322573","volume":"9","author":"DA Bennett","year":"2012","unstructured":"Bennett DA, Schneider JA, Arvanitakis Z, Wilson RS (2012) Overview and findings from the religious orders study. Curr Alzheimer Res 9:628\u2013645. https:\/\/doi.org\/10.2174\/156720512801322573","journal-title":"Curr Alzheimer Res"},{"key":"2431_CR9","doi-asserted-by":"publisher","first-page":"646","DOI":"10.2174\/156720512801322663","volume":"9","author":"DA Bennett","year":"2012","unstructured":"Bennett DA, Schneider JA, Buchman AS, Barnes LL, Boyle PA, Wilson RS (2012) Overview and findings from the rush Memory and Aging Project. Curr Alzheimer Res 9:646\u2013663. https:\/\/doi.org\/10.2174\/156720512801322663","journal-title":"Curr Alzheimer Res"},{"key":"2431_CR10","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1159\/000490349","volume":"65","author":"H Benveniste","year":"2019","unstructured":"Benveniste H, Liu X, Koundal S, Sanggaard S, Lee H, Wardlaw J (2019) The glymphatic system and waste clearance with brain aging: a review. Gerontology 65:106\u2013119. https:\/\/doi.org\/10.1159\/000490349","journal-title":"Gerontology"},{"key":"2431_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000585","volume":"18","author":"P Bhattarai","year":"2020","unstructured":"Bhattarai P, Cosacak MI, Mashkaryan V, Demir S, Popova S, Govindarajan N et al (2020) Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer\u2019s model of adult zebrafish brain. PLoS Biol 18:e3000585. https:\/\/doi.org\/10.1371\/journal.pbio.3000585","journal-title":"PLoS Biol"},{"key":"2431_CR12","doi-asserted-by":"publisher","DOI":"10.3791\/56014","author":"P Bhattarai","year":"2017","unstructured":"Bhattarai P, Thomas AK, Cosacak MI, Papadimitriou C, Mashkaryan V, Zhang Y et al (2017) Modeling amyloid-\u03b242 toxicity and neurodegeneration in adult zebrafish brain. J Vis Exp. https:\/\/doi.org\/10.3791\/56014","journal-title":"J Vis Exp"},{"key":"2431_CR13","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1016\/j.celrep.2016.09.075","volume":"17","author":"P Bhattarai","year":"2016","unstructured":"Bhattarai P, Thomas AK, Papadimitriou C, Cosacak MI, Mashkaryan V, Froc C et al (2016) IL4\/STAT6 signaling activates neural stem cell proliferation and neurogenesis upon Amyloid-\u03b242 aggregation in adult zebrafish brain. Cell Rep 17:941\u2013948. https:\/\/doi.org\/10.1016\/j.celrep.2016.09.075","journal-title":"Cell Rep"},{"key":"2431_CR14","doi-asserted-by":"publisher","DOI":"10.1080\/23262133.2017.1322666","volume":"4","author":"P Bhattarai","year":"2017","unstructured":"Bhattarai P, Thomas AK, Zhang Y, Kizil C (2017) The effects of aging on Amyloid-\u03b242-induced neurodegeneration and regeneration in adult zebrafish brain. Neurogenesis 4:e1322666. https:\/\/doi.org\/10.1080\/23262133.2017.1322666","journal-title":"Neurogenesis"},{"key":"2431_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0112-7","author":"JC Bis","year":"2018","unstructured":"Bis JC, Jian X, Kunkle BW, Chen Y, Hamilton-Nelson KL, Bush WS et al (2018) Whole exome sequencing study identifies novel rare and common Alzheimer\u2019s-Associated variants involved in immune response and transcriptional regulation. Mol Psychiatry. https:\/\/doi.org\/10.1038\/s41380-018-0112-7","journal-title":"Mol Psychiatry"},{"key":"2431_CR16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.neurobiolaging.2017.01.017","volume":"53","author":"WD Brenowitz","year":"2017","unstructured":"Brenowitz WD, Keene CD, Hawes SE, Hubbard RA, Longstreth WT Jr, Woltjer RL et al (2017) Alzheimer\u2019s disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples. Neurobiol Aging 53:83\u201392. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2017.01.017","journal-title":"Neurobiol Aging"},{"key":"2431_CR17","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1007\/s00401-018-1928-6","volume":"137","author":"IJ Broce","year":"2019","unstructured":"Broce IJ, Tan CH, Fan CC, Jansen I, Savage JE, Witoelar A et al (2019) Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer\u2019s disease. Acta Neuropathol 137:209\u2013226. https:\/\/doi.org\/10.1007\/s00401-018-1928-6","journal-title":"Acta Neuropathol"},{"key":"2431_CR18","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/s0896-6273(00)80781-3","volume":"23","author":"TG Bush","year":"1999","unstructured":"Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN et al (1999) Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 23:297\u2013308. https:\/\/doi.org\/10.1016\/s0896-6273(00)80781-3","journal-title":"Neuron"},{"key":"2431_CR19","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.neurobiolaging.2018.02.009","volume":"67","author":"FE Cambronero","year":"2018","unstructured":"Cambronero FE, Liu D, Neal JE, Moore EE, Gifford KA, Terry JG et al (2018) APOE genotype modifies the association between central arterial stiffening and cognition in older adults. Neurobiol Aging 67:120\u2013127. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2018.02.009","journal-title":"Neurobiol Aging"},{"key":"2431_CR20","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1002\/sim.8037","volume":"38","author":"T Yang","year":"2019","unstructured":"Yang T, Chen H, Tang H, Li D, Wei P (2019) A powerful and data-adaptive test for rare-variant-based gene-environment interaction analysis. Stat Med 38:1230\u20131244. https:\/\/doi.org\/10.1002\/sim.8037","journal-title":"Stat Med"},{"key":"2431_CR21","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/s43587-022-00181-4","volume":"2","author":"X Chen","year":"2022","unstructured":"Chen X, Liu X, Koundal S, Elkin R, Zhu X, Monte B et al (2022) Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries. Nat Aging 2:214\u2013223. https:\/\/doi.org\/10.1038\/s43587-022-00181-4","journal-title":"Nat Aging"},{"key":"2431_CR22","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1159\/000324134","volume":"31","author":"D Cheng","year":"2011","unstructured":"Cheng D, Noble J, Tang MX, Schupf N, Mayeux R, Luchsinger JA (2011) Type 2 diabetes and late-onset Alzheimer\u2019s disease. Dement Geriatr Cogn Disord 31:424\u2013430. https:\/\/doi.org\/10.1159\/000324134","journal-title":"Dement Geriatr Cogn Disord"},{"key":"2431_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035591","volume":"7","author":"JW Cole","year":"2012","unstructured":"Cole JW, Stine OC, Liu X, Pratap A, Cheng Y, Tallon LJ et al (2012) Rare variants in ischemic stroke: an exome pilot study. PLoS ONE 7:e35591. https:\/\/doi.org\/10.1371\/journal.pone.0035591","journal-title":"PLoS ONE"},{"issue":"1307\u20131318","key":"2431_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.090","volume":"27","author":"MI Cosacak","year":"2019","unstructured":"Cosacak MI, Bhattarai P, Reinhardt S, Petzold A, Dahl A, Zhang Y et al (2019) Single-cell transcriptomics analyses of neural stem cell heterogeneity and contextual plasticity in a zebrafish brain model of amyloid toxicity. Cell Rep 27(1307\u20131318):e1303. https:\/\/doi.org\/10.1016\/j.celrep.2019.03.090","journal-title":"Cell Rep"},{"key":"2431_CR25","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020412","volume":"7","author":"R Daneman","year":"2015","unstructured":"Daneman R, Prat A (2015) The blood-brain barrier. Cold Spring Harb Perspect Biol 7:a020412. https:\/\/doi.org\/10.1101\/cshperspect.a020412","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2431_CR26","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/ng.3656","volume":"48","author":"S Das","year":"2016","unstructured":"Das S, Forer L, Sch\u00f6nherr S, Sidore C, Locke AE, Kwong A et al (2016) Next-generation genotype imputation service and methods. Nat Genet 48:1284\u20131287. https:\/\/doi.org\/10.1038\/ng.3656","journal-title":"Nat Genet"},{"key":"2431_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.142","volume":"5","author":"PL De Jager","year":"2018","unstructured":"De Jager PL, Ma Y, McCabe C, Xu J, Vardarajan BN, Felsky D et al (2018) A multi-omic atlas of the human frontal cortex for aging and Alzheimer\u2019s disease research. Sci Data 5:180142. https:\/\/doi.org\/10.1038\/sdata.2018.142","journal-title":"Sci Data"},{"key":"2431_CR28","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nmeth.2307","volume":"10","author":"O Delaneau","year":"2013","unstructured":"Delaneau O, Zagury JF, Marchini J (2013) Improved whole-chromosome phasing for disease and population genetic studies. Nat Methods 10:5\u20136. https:\/\/doi.org\/10.1038\/nmeth.2307","journal-title":"Nat Methods"},{"key":"2431_CR29","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1042\/CS20160727","volume":"131","author":"J Duncombe","year":"2017","unstructured":"Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria RN, Horsburgh K (2017) Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clin Sci (Lond) 131:2451\u20132468. https:\/\/doi.org\/10.1042\/CS20160727","journal-title":"Clin Sci (Lond)"},{"key":"2431_CR30","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.devcel.2006.05.001","volume":"10","author":"J Faix","year":"2006","unstructured":"Faix J, Grosse R (2006) Staying in shape with formins. Dev Cell 10:693\u2013706. https:\/\/doi.org\/10.1016\/j.devcel.2006.05.001","journal-title":"Dev Cell"},{"key":"2431_CR31","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1212\/WNL.0000000000002909","volume":"87","author":"JM Farfel","year":"2016","unstructured":"Farfel JM, Yu L, Buchman AS, Schneider JA, De Jager PL, Bennett DA (2016) Relation of genomic variants for Alzheimer disease dementia to common neuropathologies. Neurology 87:489\u2013496. https:\/\/doi.org\/10.1212\/WNL.0000000000002909","journal-title":"Neurology"},{"issue":"Suppl 1","key":"2431_CR32","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.1089\/zeb.2015.1205","volume":"13","author":"R Geisler","year":"2016","unstructured":"Geisler R, Borel N, Ferg M, Maier JV, Strahle U (2016) Maintenance of zebrafish lines at the European Zebrafish Resource Center. Zebrafish 13(Suppl 1):S19-23. https:\/\/doi.org\/10.1089\/zeb.2015.1205","journal-title":"Zebrafish"},{"key":"2431_CR33","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1001\/archinte.163.13.1524","volume":"163","author":"D Gustafson","year":"2003","unstructured":"Gustafson D, Rothenberg E, Blennow K, Steen B, Skoog I (2003) An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med 163:1524\u20131528. https:\/\/doi.org\/10.1001\/archinte.163.13.1524","journal-title":"Arch Intern Med"},{"key":"2431_CR34","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s00401-018-1834-y","volume":"135","author":"M Hecht","year":"2018","unstructured":"Hecht M, Kramer LM, von Arnim CAF, Otto M, Thal DR (2018) Capillary cerebral amyloid angiopathy in Alzheimer\u2019s disease: association with allocortical\/hippocampal microinfarcts and cognitive decline. Acta Neuropathol 135:681\u2013694. https:\/\/doi.org\/10.1007\/s00401-018-1834-y","journal-title":"Acta Neuropathol"},{"key":"2431_CR35","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.jalz.2015.02.012","volume":"12","author":"TJ Hohman","year":"2016","unstructured":"Hohman TJ, Cooke-Bailey JN, Reitz C, Jun G, Naj A, Beecham GW et al (2016) Global and local ancestry in African\u2013Americans: implications for Alzheimer\u2019s disease risk. Alzheimers Dement 12:233\u2013243. https:\/\/doi.org\/10.1016\/j.jalz.2015.02.012","journal-title":"Alzheimers Dement"},{"key":"2431_CR36","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.brainres.2005.07.071","volume":"1058","author":"LC Hudson","year":"2005","unstructured":"Hudson LC, Bragg DC, Tompkins MB, Meeker RB (2005) Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells. Brain Res 1058:148\u2013160. https:\/\/doi.org\/10.1016\/j.brainres.2005.07.071","journal-title":"Brain Res"},{"key":"2431_CR37","doi-asserted-by":"crossref","unstructured":"\u0130s O, Wang X, Patel T, Quicksall Z, Heckman M, White L et al (2022) Single nuclei transcriptome reveals perturbed brain vascular molecules in Alzheimer\u2019s disease. BioRxiv, City","DOI":"10.1101\/2021.12.28.474255"},{"key":"2431_CR38","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack Jr","year":"2018","unstructured":"Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. Alzheimers Dement 14:535\u2013562. https:\/\/doi.org\/10.1016\/j.jalz.2018.02.018","journal-title":"Alzheimers Dement"},{"key":"2431_CR39","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1016\/j.neurobiolaging.2015.05.010","volume":"36","author":"C Janus","year":"2015","unstructured":"Janus C, Flores AY, Xu G, Borchelt DR (2015) Behavioral abnormalities in APPSwe\/PS1dE9 mouse model of AD-like pathology: comparative analysis across multiple behavioral domains. Neurobiol Aging 36:2519\u20132532. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2015.05.010","journal-title":"Neurobiol Aging"},{"key":"2431_CR40","doi-asserted-by":"publisher","first-page":"5199","DOI":"10.1242\/dev.02087","volume":"132","author":"SW Jin","year":"2005","unstructured":"Jin SW, Beis D, Mitchell T, Chen JN, Stainier DY (2005) Cellular and molecular analyses of vascular tube and lumen formation in zebrafish. Development 132:5199\u20135209. https:\/\/doi.org\/10.1242\/dev.02087","journal-title":"Development"},{"key":"2431_CR41","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/mp.2015.23","volume":"21","author":"G Jun","year":"2016","unstructured":"Jun G, Ibrahim-Verbaas CA, Vronskaya M, Lambert JC, Chung J, Naj AC et al (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108\u2013117. https:\/\/doi.org\/10.1038\/mp.2015.23","journal-title":"Mol Psychiatry"},{"key":"2431_CR42","doi-asserted-by":"publisher","first-page":"135","DOI":"10.2147\/CLEP.S30621","volume":"5","author":"BN Justin","year":"2013","unstructured":"Justin BN, Turek M, Hakim AM (2013) Heart disease as a risk factor for dementia. Clin Epidemiol 5:135\u2013145. https:\/\/doi.org\/10.2147\/CLEP.S30621","journal-title":"Clin Epidemiol"},{"key":"2431_CR43","doi-asserted-by":"publisher","first-page":"9791","DOI":"10.1038\/s41598-017-09952-1","volume":"7","author":"F Kage","year":"2017","unstructured":"Kage F, Steffen A, Ellinger A, Ranftler C, Gehre C, Brakebusch C et al (2017) FMNL2 and -3 regulate Golgi architecture and anterograde transport downstream of Cdc42. Sci Rep 7:9791. https:\/\/doi.org\/10.1038\/s41598-017-09952-1","journal-title":"Sci Rep"},{"key":"2431_CR44","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00401-017-1717-7","volume":"134","author":"A Kapasi","year":"2017","unstructured":"Kapasi A, DeCarli C, Schneider JA (2017) Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol 134:171\u2013186. https:\/\/doi.org\/10.1007\/s00401-017-1717-7","journal-title":"Acta Neuropathol"},{"key":"2431_CR45","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1159\/000026209","volume":"18","author":"DE Kargman","year":"1999","unstructured":"Kargman DE, Sacco RL, Boden-Albala B, Paik MC, Hauser WA, Shea S (1999) Validity of telephone interview data for vascular disease risk factors in a racially mixed urban community: the Northern Manhattan Stroke Study. Neuroepidemiology 18:174\u2013184. https:\/\/doi.org\/10.1159\/000026209","journal-title":"Neuroepidemiology"},{"key":"2431_CR46","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s40478-020-01042-0","volume":"8","author":"SH Kim","year":"2020","unstructured":"Kim SH, Ahn JH, Yang H, Lee P, Koh GY, Jeong Y (2020) Cerebral amyloid angiopathy aggravates perivascular clearance impairment in an Alzheimer\u2019s disease mouse model. Acta Neuropathol Commun 8:181. https:\/\/doi.org\/10.1186\/s40478-020-01042-0","journal-title":"Acta Neuropathol Commun"},{"key":"2431_CR47","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.1093\/brain\/awv327","volume":"138","author":"IF Kimbrough","year":"2015","unstructured":"Kimbrough IF, Robel S, Roberson ED, Sontheimer H (2015) Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer\u2019s disease. Brain 138:3716\u20133733. https:\/\/doi.org\/10.1093\/brain\/awv327","journal-title":"Brain"},{"key":"2431_CR48","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s40139-018-0158-x","volume":"6","author":"C Kizil","year":"2018","unstructured":"Kizil C (2018) Mechanisms of pathology-induced neural stem cell plasticity and neural regeneration in adult zebrafish brain. Curr Pathobiol Rep 6:71\u201377. https:\/\/doi.org\/10.1007\/s40139-018-0158-x","journal-title":"Curr Pathobiol Rep"},{"key":"2431_CR49","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.ydbio.2008.09.032","volume":"325","author":"C Kizil","year":"2009","unstructured":"Kizil C, Otto GW, Geisler R, Nusslein-Volhard C, Antos CL (2009) Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration. Dev Biol 325:329\u2013340. https:\/\/doi.org\/10.1016\/j.ydbio.2008.09.032","journal-title":"Dev Biol"},{"key":"2431_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01526-6","author":"C Kizil","year":"2022","unstructured":"Kizil C, Sariya S, Kim YA, Rajabli F, Martin E, Reyes-Dumeyer D et al (2022) Admixture mapping of Alzheimer\u2019s disease in Caribbean Hispanics identifies a new locus on 22q13.1. Mol Psychiatry. https:\/\/doi.org\/10.1038\/s41380-022-01526-6","journal-title":"Mol Psychiatry"},{"key":"2431_CR51","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1089\/zeb.2017.1508","volume":"14","author":"A Kohler","year":"2017","unstructured":"Kohler A, Collymore C, Finger-Baier K, Geisler R, Kaufmann L, Pounder KC et al (2017) Report of workshop on Euthanasia for zebrafish\u2014a matter of welfare and science. Zebrafish 14:547\u2013551. https:\/\/doi.org\/10.1089\/zeb.2017.1508","journal-title":"Zebrafish"},{"key":"2431_CR52","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","volume":"51","author":"BW Kunkle","year":"2019","unstructured":"Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC et al (2019) Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing. Nat Genet 51:414\u2013430. https:\/\/doi.org\/10.1038\/s41588-019-0358-2","journal-title":"Nat Genet"},{"key":"2431_CR53","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","volume":"51","author":"BW Kunkle","year":"2019","unstructured":"Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC et al (2019) Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates Abeta, tau, immunity and lipid processing. Nat Genet 51:414\u2013430. https:\/\/doi.org\/10.1038\/s41588-019-0358-2","journal-title":"Nat Genet"},{"key":"2431_CR54","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1038\/mp.2012.14","volume":"18","author":"JC Lambert","year":"2013","unstructured":"Lambert JC, Grenier-Boley B, Harold D, Zelenika D, Chouraki V, Kamatani Y et al (2013) Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer\u2019s disease. Mol Psychiatry 18:461\u2013470. https:\/\/doi.org\/10.1038\/mp.2012.14","journal-title":"Mol Psychiatry"},{"key":"2431_CR55","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/1471-2318-14-36","volume":"14","author":"R Lathe","year":"2014","unstructured":"Lathe R, Sapronova A, Kotelevtsev Y (2014) Atherosclerosis and Alzheimer\u2014diseases with a common cause? Inflammation, oxysterols, vasculature. BMC Geriatr 14:36. https:\/\/doi.org\/10.1186\/1471-2318-14-36","journal-title":"BMC Geriatr"},{"key":"2431_CR56","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1093\/biostatistics\/kxt006","volume":"14","author":"X Lin","year":"2013","unstructured":"Lin X, Lee S, Christiani DC, Lin X (2013) Test for interactions between a genetic marker set and environment in generalized linear models. Biostatistics 14:667\u2013681. https:\/\/doi.org\/10.1093\/biostatistics\/kxt006","journal-title":"Biostatistics"},{"key":"2431_CR57","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1097\/WAD.0b013e318222f0d4","volume":"26","author":"JA Luchsinger","year":"2012","unstructured":"Luchsinger JA, Cheng D, Tang MX, Schupf N, Mayeux R (2012) Central obesity in the elderly is related to late-onset Alzheimer disease. Alzheimer Dis Assoc Disord 26:101\u2013105. https:\/\/doi.org\/10.1097\/WAD.0b013e318222f0d4","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2431_CR58","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1212\/01.wnl.0000172914.08967.dc","volume":"65","author":"JA Luchsinger","year":"2005","unstructured":"Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R (2005) Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology 65:545\u2013551. https:\/\/doi.org\/10.1212\/01.wnl.0000172914.08967.dc","journal-title":"Neurology"},{"key":"2431_CR59","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1093\/aje\/154.7.635","volume":"154","author":"JA Luchsinger","year":"2001","unstructured":"Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R (2001) Diabetes mellitus and risk of Alzheimer\u2019s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 154:635\u2013641. https:\/\/doi.org\/10.1093\/aje\/154.7.635","journal-title":"Am J Epidemiol"},{"key":"2431_CR60","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul A, Mychaleckyj JC, Rich SS, Daly K, Sale M, Chen WM (2010) Robust relationship inference in genome-wide association studies. Bioinformatics (Oxford, England) 26:2867\u20132873. https:\/\/doi.org\/10.1093\/bioinformatics\/btq559","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2431_CR61","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jalz.2011.03.005","volume":"7","author":"GM McKhann","year":"2011","unstructured":"McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH et al (2011) The diagnosis of dementia due to Alzheimer\u2019s disease: recommendations from the National Institute on Aging-Alzheimer\u2019s Association workgroups on diagnostic guidelines for Alzheimer\u2019s disease. Alzheimers Dement 7:263\u2013269. https:\/\/doi.org\/10.1016\/j.jalz.2011.03.005","journal-title":"Alzheimers Dement"},{"key":"2431_CR62","doi-asserted-by":"publisher","first-page":"1794","DOI":"10.1038\/s41467-022-29475-2","volume":"13","author":"WA Mills 3rd","year":"2022","unstructured":"Mills WA 3rd, Woo AM, Jiang S, Martin J, Surendran D, Bergstresser M et al (2022) Astrocyte plasticity in mice ensures continued endfoot coverage of cerebral blood vessels following injury and declines with age. Nat Commun 13:1794. https:\/\/doi.org\/10.1038\/s41467-022-29475-2","journal-title":"Nat Commun"},{"key":"2431_CR63","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.nbd.2011.01.021","volume":"43","author":"RA Nixon","year":"2011","unstructured":"Nixon RA, Yang DS (2011) Autophagy failure in Alzheimer\u2019s disease\u2013locating the primary defect. Neurobiol Dis 43:38\u201345. https:\/\/doi.org\/10.1016\/j.nbd.2011.01.021","journal-title":"Neurobiol Dis"},{"key":"2431_CR64","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1212\/01.wnl.0000038910.46217.aa","volume":"60","author":"F Nourhashemi","year":"2003","unstructured":"Nourhashemi F, Deschamps V, Larrieu S, Letenneur L, Dartigues JF, Barberger-Gateau P et al (2003) Body mass index and incidence of dementia: the PAQUID study. Neurology 60:117\u2013119. https:\/\/doi.org\/10.1212\/01.wnl.0000038910.46217.aa","journal-title":"Neurology"},{"key":"2431_CR65","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1161\/01.str.28.2.316","volume":"28","author":"A Ott","year":"1997","unstructured":"Ott A, Breteler MM, de Bruyne MC, van Harskamp F, Grobbee DE, Hofman A (1997) Atrial fibrillation and dementia in a population-based study. The Rotterdam Study. Stroke 28:316\u2013321. https:\/\/doi.org\/10.1161\/01.str.28.2.316","journal-title":"Stroke"},{"issue":"85\u2013101","key":"2431_CR66","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.06.005","volume":"46","author":"C Papadimitriou","year":"2018","unstructured":"Papadimitriou C, Celikkaya H, Cosacak MI, Mashkaryan V, Bray L, Bhattarai P et al (2018) 3D culture method for Alzheimer\u2019s disease modeling reveals interleukin-4 rescues Abeta42-induced loss of human neural stem cell plasticity. Dev Cell 46(85\u2013101):e108. https:\/\/doi.org\/10.1016\/j.devcel.2018.06.005","journal-title":"Dev Cell"},{"key":"2431_CR67","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/2045-8118-8-21","volume":"8","author":"CL Pascale","year":"2011","unstructured":"Pascale CL, Miller MC, Chiu C, Boylan M, Caralopoulos IN, Gonzalez L et al (2011) Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent. Fluids Barr CNS 8:21. https:\/\/doi.org\/10.1186\/2045-8118-8-21","journal-title":"Fluids Barr CNS"},{"key":"2431_CR68","doi-asserted-by":"publisher","first-page":"3161","DOI":"10.1083\/jcb.201701045","volume":"216","author":"X Qu","year":"2017","unstructured":"Qu X, Yuan FN, Corona C, Pasini S, Pero ME, Gundersen GG et al (2017) Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Abeta1-42 synaptotoxicity. J Cell Biol 216:3161\u20133178. https:\/\/doi.org\/10.1083\/jcb.201701045","journal-title":"J Cell Biol"},{"key":"2431_CR69","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/j.stemcr.2019.01.015","volume":"12","author":"L Reinhardt","year":"2019","unstructured":"Reinhardt L, Kordes S, Reinhardt P, Glatza M, Baumann M, Drexler HCA et al (2019) Dual inhibition of GSK3beta and CDK5 protects the cytoskeleton of neurons from neuroinflammatory-mediated degeneration in vitro and in vivo. Stem Cell Rep 12:502\u2013517. https:\/\/doi.org\/10.1016\/j.stemcr.2019.01.015","journal-title":"Stem Cell Rep"},{"key":"2431_CR70","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1001\/archneurol.2010.136","volume":"67","author":"C Reitz","year":"2010","unstructured":"Reitz C, Tang MX, Schupf N, Manly JJ, Mayeux R, Luchsinger JA (2010) A summary risk score for the prediction of Alzheimer disease in elderly persons. Arch Neurol 67:835\u2013841. https:\/\/doi.org\/10.1001\/archneurol.2010.136","journal-title":"Arch Neurol"},{"key":"2431_CR71","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1093\/bib\/bby039","volume":"20","author":"E Rojano","year":"2019","unstructured":"Rojano E, Seoane P, Ranea JAG, Perkins JR (2019) Regulatory variants: from detection to predicting impact. Brief Bioinform 20:1639\u20131654. https:\/\/doi.org\/10.1093\/bib\/bby039","journal-title":"Brief Bioinform"},{"key":"2431_CR72","doi-asserted-by":"publisher","first-page":"672","DOI":"10.3389\/fgene.2018.00672","volume":"9","author":"AB Rose","year":"2018","unstructured":"Rose AB (2018) Introns as gene regulators: a brick on the accelerator. Front Genet 9:672. https:\/\/doi.org\/10.3389\/fgene.2018.00672","journal-title":"Front Genet"},{"key":"2431_CR73","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1111\/jnc.13932","volume":"140","author":"A Salminen","year":"2017","unstructured":"Salminen A, Kauppinen A, Kaarniranta K (2017) Hypoxia\/ischemia activate processing of amyloid precursor protein: impact of vascular dysfunction in the pathogenesis of Alzheimer\u2019s disease. J Neurochem 140:536\u2013549. https:\/\/doi.org\/10.1111\/jnc.13932","journal-title":"J Neurochem"},{"key":"2431_CR74","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1212\/01.wnl.0000271090.28148.24","volume":"69","author":"JA Schneider","year":"2007","unstructured":"Schneider JA, Arvanitakis Z, Bang W, Bennett DA (2007) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69:2197\u20132204. https:\/\/doi.org\/10.1212\/01.wnl.0000271090.28148.24","journal-title":"Neurology"},{"key":"2431_CR75","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1161\/01.STR.0000160747.27470.2a","volume":"36","author":"JA Schneider","year":"2005","unstructured":"Schneider JA, Bienias JL, Wilson RS, Berry-Kravis E, Evans DA, Bennett DA (2005) The apolipoprotein E epsilon4 allele increases the odds of chronic cerebral infarction [corrected] detected at autopsy in older persons. Stroke 36:954\u2013959. https:\/\/doi.org\/10.1161\/01.STR.0000160747.27470.2a","journal-title":"Stroke"},{"key":"2431_CR76","doi-asserted-by":"publisher","first-page":"4483","DOI":"10.1073\/pnas.1721694115","volume":"115","author":"E Shokri-Kojori","year":"2018","unstructured":"Shokri-Kojori E, Wang GJ, Wiers CE, Demiral SB, Guo M, Kim SW et al (2018) beta-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci USA 115:4483\u20134488. https:\/\/doi.org\/10.1073\/pnas.1721694115","journal-title":"Proc Natl Acad Sci USA"},{"key":"2431_CR77","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102748","author":"T Siddiqui","year":"2021","unstructured":"Siddiqui T, Bhattarai P, Popova S, Cosacak MI, Sariya S, Zhang Y et al (2021) KYNA\/Ahr signaling suppresses neural stem cell plasticity and neurogenesis in adult zebrafish model of Alzheimer\u2019s disease. Cells. https:\/\/doi.org\/10.3390\/cells10102748","journal-title":"Cells"},{"key":"2431_CR78","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/s0140-6736(96)90608-x","volume":"347","author":"I Skoog","year":"1996","unstructured":"Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson LA, Nilsson L et al (1996) 15-year longitudinal study of blood pressure and dementia. Lancet 347:1141\u20131145. https:\/\/doi.org\/10.1016\/s0140-6736(96)90608-x","journal-title":"Lancet"},{"key":"2431_CR79","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.reprotox.2011.06.121","volume":"33","author":"U Strahle","year":"2012","unstructured":"Strahle U, Scholz S, Geisler R, Greiner P, Hollert H, Rastegar S et al (2012) Zebrafish embryos as an alternative to animal experiments\u2013a commentary on the definition of the onset of protected life stages in animal welfare regulations. Reprod Toxicol 33:128\u2013132. https:\/\/doi.org\/10.1016\/j.reprotox.2011.06.121","journal-title":"Reprod Toxicol"},{"key":"2431_CR80","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":"2431_CR81","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1161\/HYPERTENSIONAHA.114.03617","volume":"65","author":"Z Sun","year":"2015","unstructured":"Sun Z (2015) Aging, arterial stiffness, and hypertension. Hypertension 65:252\u2013256. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.114.03617","journal-title":"Hypertension"},{"key":"2431_CR82","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrneurol.2017.188","volume":"14","author":"MD Sweeney","year":"2018","unstructured":"Sweeney MD, Sagare AP, Zlokovic BV (2018) Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat Rev Neurol 14:133\u2013150. https:\/\/doi.org\/10.1038\/nrneurol.2017.188","journal-title":"Nat Rev Neurol"},{"key":"2431_CR83","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1001\/jama.279.10.751","volume":"279","author":"MX Tang","year":"1998","unstructured":"Tang MX, Stern Y, Marder K, Bell K, Gurland B, Lantigua R et al (1998) The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics. JAMA 279:751\u2013755. https:\/\/doi.org\/10.1001\/jama.279.10.751","journal-title":"JAMA"},{"key":"2431_CR84","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrneurol.2015.119","volume":"11","author":"JM Tarasoff-Conway","year":"2015","unstructured":"Tarasoff-Conway JM, Carare RO, Osorio RS, Glodzik L, Butler T, Fieremans E et al (2015) Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol 11:457\u2013470. https:\/\/doi.org\/10.1038\/nrneurol.2015.119","journal-title":"Nat Rev Neurol"},{"key":"2431_CR85","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v059.i05","volume":"59","author":"D Tingley","year":"2014","unstructured":"Tingley D, Yamamoto T, Hirose K, Imai K, Keele L (2014) Mediation: R package for causal mediation analysis. J Stat Softw 59:1\u201338","journal-title":"J Stat Softw"},{"key":"2431_CR86","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1001\/jamaneurol.2016.2539","volume":"73","author":"G Tosto","year":"2016","unstructured":"Tosto G, Bird TD, Bennett DA, Boeve BF, Brickman AM, Cruchaga C et al (2016) The role of cardiovascular risk factors and stroke in familial Alzheimer disease. JAMA Neurol 73:1231\u20131237. https:\/\/doi.org\/10.1001\/jamaneurol.2016.2539","journal-title":"JAMA Neurol"},{"key":"2431_CR87","doi-asserted-by":"publisher","first-page":"H1","DOI":"10.1152\/ajpheart.00581.2016","volume":"312","author":"P Toth","year":"2017","unstructured":"Toth P, Tarantini S, Csiszar A, Ungvari Z (2017) Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging. Am J Physiol Heart Circ Physiol 312:H1\u2013H20. https:\/\/doi.org\/10.1152\/ajpheart.00581.2016","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2431_CR88","doi-asserted-by":"publisher","unstructured":"Traylor M, Adib-Samii P, Harold D, Alzheimer's Disease Neuroimaging I, International Stroke Genetics Consortium UKYLSDNAr, Dichgans M, Williams J, Lewis CM, Markus HS, Metastrokeet al (2016) Shared genetic contribution to ischaemic stroke and Alzheimer's disease. Ann Neurol 79:739\u2013747. https:\/\/doi.org\/10.1002\/ana.24621","DOI":"10.1002\/ana.24621"},{"key":"2431_CR89","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/S2213-8587(19)30405-X","volume":"8","author":"TT van Sloten","year":"2020","unstructured":"van Sloten TT, Sedaghat S, Carnethon MR, Launer LJ, Stehouwer CDA (2020) Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Lancet Diabetes Endocrinol 8:325\u2013336. https:\/\/doi.org\/10.1016\/S2213-8587(19)30405-X","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2431_CR90","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1001\/jamaneurol.2013.5570","volume":"71","author":"BN Vardarajan","year":"2014","unstructured":"Vardarajan BN, Faber KM, Bird TD, Bennett DA, Rosenberg R, Boeve BF et al (2014) Age-specific incidence rates for dementia and Alzheimer disease in NIA-LOAD\/NCRAD and EFIGA families: National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease\/National Cell Repository for Alzheimer Disease (NIA-LOAD\/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA). JAMA Neurol 71:315\u2013323. https:\/\/doi.org\/10.1001\/jamaneurol.2013.5570","journal-title":"JAMA Neurol"},{"key":"2431_CR91","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.devcel.2014.11.024","volume":"32","author":"Y Wakayama","year":"2015","unstructured":"Wakayama Y, Fukuhara S, Ando K, Matsuda M, Mochizuki N (2015) Cdc42 mediates Bmp-induced sprouting angiogenesis through Fmnl3-driven assembly of endothelial filopodia in zebrafish. Dev Cell 32:109\u2013122. https:\/\/doi.org\/10.1016\/j.devcel.2014.11.024","journal-title":"Dev Cell"},{"key":"2431_CR92","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1038\/nprot.2006.354","volume":"1","author":"HJ Waldvogel","year":"2006","unstructured":"Waldvogel HJ, Curtis MA, Baer K, Rees MI, Faull RL (2006) Immunohistochemical staining of post-mortem adult human brain sections. Nat Protoc 1:2719\u20132732. https:\/\/doi.org\/10.1038\/nprot.2006.354","journal-title":"Nat Protoc"},{"key":"2431_CR93","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107908","volume":"32","author":"YW Wan","year":"2020","unstructured":"Wan YW, Al-Ouran R, Mangleburg CG, Perumal TM, Lee TV, Allison K et al (2020) Meta-analysis of the alzheimer\u2019s disease human brain transcriptome and functional dissection in mouse models. Cell Rep 32:107908. https:\/\/doi.org\/10.1016\/j.celrep.2020.107908","journal-title":"Cell Rep"},{"key":"2431_CR94","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.185","volume":"5","author":"M Wang","year":"2018","unstructured":"Wang M, Beckmann ND, Roussos P, Wang E, Zhou X, Wang Q et al (2018) The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer\u2019s disease. Sci Data 5:180185. https:\/\/doi.org\/10.1038\/sdata.2018.185","journal-title":"Sci Data"},{"key":"2431_CR95","doi-asserted-by":"publisher","first-page":"27231","DOI":"10.1038\/srep27231","volume":"6","author":"PH Weng","year":"2016","unstructured":"Weng PH, Chen JH, Chen TF, Sun Y, Wen LL, Yip PK et al (2016) CHRNA7 polymorphisms and dementia risk: interactions with apolipoprotein epsilon4 and cigarette smoking. Sci Rep 6:27231. https:\/\/doi.org\/10.1038\/srep27231","journal-title":"Sci Rep"},{"key":"2431_CR96","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics (Oxford, England) 26:2190\u20132191. https:\/\/doi.org\/10.1093\/bioinformatics\/btq340","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2431_CR97","doi-asserted-by":"publisher","first-page":"E6962","DOI":"10.1073\/pnas.1701137114","volume":"114","author":"AM Wojtas","year":"2017","unstructured":"Wojtas AM, Kang SS, Olley BM, Gatherer M, Shinohara M, Lozano PA et al (2017) Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways. Proc Natl Acad Sci USA 114:E6962\u2013E6971. https:\/\/doi.org\/10.1073\/pnas.1701137114","journal-title":"Proc Natl Acad Sci USA"},{"key":"2431_CR98","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1126\/science.1241224","volume":"342","author":"L Xie","year":"2013","unstructured":"Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M et al (2013) Sleep drives metabolite clearance from the adult brain. Science 342:373\u2013377. https:\/\/doi.org\/10.1126\/science.1241224","journal-title":"Science"},{"key":"2431_CR99","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091965","author":"Y Yamazaki","year":"2017","unstructured":"Yamazaki Y, Kanekiyo T (2017) Blood\u2013brain barrier dysfunction and the pathogenesis of Alzheimer\u2019s disease. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms18091965","journal-title":"Int J Mol Sci"},{"key":"2431_CR100","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.ydbio.2006.10.020","volume":"301","author":"SY Yeo","year":"2007","unstructured":"Yeo SY, Kim M, Kim HS, Huh TL, Chitnis AB (2007) Fluorescent protein expression driven by her4 regulatory elements reveals the spatiotemporal pattern of Notch signaling in the nervous system of zebrafish embryos. Dev Biol 301:555\u2013567. https:\/\/doi.org\/10.1016\/j.ydbio.2006.10.020","journal-title":"Dev Biol"},{"key":"2431_CR101","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1001\/jamapsychiatry.2020.1807","volume":"77","author":"L Yu","year":"2020","unstructured":"Yu L, Tasaki S, Schneider JA, Arfanakis K, Duong DM, Wingo AP et al (2020) Cortical proteins associated with cognitive resilience in community-dwelling older persons. JAMA Psychiat 77:1172\u20131180. https:\/\/doi.org\/10.1001\/jamapsychiatry.2020.1807","journal-title":"JAMA Psychiat"},{"key":"2431_CR102","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.nbd.2016.07.007","volume":"107","author":"E Zenaro","year":"2017","unstructured":"Zenaro E, Piacentino G, Constantin G (2017) The blood\u2013brain barrier in Alzheimer\u2019s disease. Neurobiol Dis 107:41\u201356. https:\/\/doi.org\/10.1016\/j.nbd.2016.07.007","journal-title":"Neurobiol Dis"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-022-02431-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-022-02431-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-022-02431-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T08:12:11Z","timestamp":1655885531000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-022-02431-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":102,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["2431"],"URL":"https:\/\/doi.org\/10.1007\/s00401-022-02431-6","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742163440.793597074","asserted-by":"object"}]},"ISSN":["0001-6322","1432-0533"],"issn-type":[{"value":"0001-6322","type":"print"},{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]},"assertion":[{"value":"2 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"C.K. has executive function in Neuron-D GmbH (Germany), which had no financial relationship to or influence on this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}