{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:30:31Z","timestamp":1792729831636,"version":"4.5.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["UK MRC (G0400074)"],"award-info":[{"award-number":["UK MRC (G0400074)"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neurovascular unit mural cells called \u2018pericytes\u2019 maintain the blood-brain barrier and local cerebral blood flow. Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 post-mortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer\u2019s disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25\u201340% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1\u2009\u00b1\u20090.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (\n                    <jats:italic>P\u2009&lt;<\/jats:italic>\n                    \u20090.001). Pericyte densities were correlated with CA1 volumes (r\u2009=\u20090.54,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection.\n                  <\/jats:p>","DOI":"10.1186\/s40478-024-01737-8","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T12:02:32Z","timestamp":1707998552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer\u2019s disease and experimental chronic cerebral hypoperfusion"],"prefix":"10.1186","volume":"12","author":[{"given":"Yoshiki","family":"Hase","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Jobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Cheong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelvin","family":"Gotama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Maffei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Hase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alhafidz","family":"Hamdan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomo","family":"Polivkoski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Horsburgh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj N.","family":"Kalaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"1737_CR1","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.1093\/brain\/awr273","volume":"134","author":"LM Allan","year":"2011","unstructured":"Allan LM, Rowan EN, Firbank MJ, Thomas AJ, Parry SW, Polvikoski TM, O\u2019Brien JT, Kalaria RN (2011) Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors. Brain 134:3716\u20133727. https:\/\/doi.org\/10.1093\/brain\/awr273","journal-title":"Brain"},{"key":"1737_CR2","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1111\/ene.13191","volume":"24","author":"F Arba","year":"2017","unstructured":"Arba F, Quinn T, Hankey GJ, Ali M, Lees KR, Inzitari D, Collaboration V (2017) Cerebral small vessel disease, medial temporal lobe atrophy and cognitive status in patients with ischaemic stroke and transient ischaemic attack. Eur J Neurol 24:276\u2013282. https:\/\/doi.org\/10.1111\/ene.13191","journal-title":"Eur J Neurol"},{"key":"1737_CR3","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1212\/01.wnl.0000141851.93193.17","volume":"63","author":"CG Ballard","year":"2004","unstructured":"Ballard CG, Morris CM, Rao H, O\u2019Brien JT, Barber R, Stephens S, Rowan E, Gibson A, Kalaria RN, Kenny RA (2004) APOE epsilon4 and cognitive decline in older stroke patients with early cognitive impairment. Neurology 63:1399\u20131402. https:\/\/doi.org\/10.1212\/01.wnl.0000141851.93193.17","journal-title":"Neurology"},{"key":"1737_CR4","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.celrep.2017.12.016","volume":"22","author":"AA Berthiaume","year":"2018","unstructured":"Berthiaume AA, Grant RI, McDowell KP, Underly RG, Hartmann DA, Levy M, Bhat NR, Shih AY (2018) Dynamic remodeling of pericytes in vivo maintains capillary coverage in the adult mouse brain. Cell Rep 22:8\u201316. https:\/\/doi.org\/10.1016\/j.celrep.2017.12.016","journal-title":"Cell Rep"},{"key":"1737_CR5","doi-asserted-by":"publisher","unstructured":"Broadhouse KM, Singh MF, Suo C, Gates N, Wen W, Brodaty H, Jain N, Wilson GC, Meiklejohn J, Singh N et al (2020) Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. Neuroimage Clin 25:102182 https:\/\/doi.org\/10.1016\/j.nicl.2020.102182","DOI":"10.1016\/j.nicl.2020.102182"},{"key":"1737_CR6","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/nan.12085","volume":"40","author":"MJ Burke","year":"2014","unstructured":"Burke MJ, Nelson L, Slade JY, Oakley AE, Khundakar AA, Kalaria RN (2014) Morphometry of the hippocampal microvasculature in post-stroke and age-related dementias. Neuropathol Appl Neurobiol 40:284\u2013295. https:\/\/doi.org\/10.1111\/nan.12085","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1737_CR7","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1111\/bpa.12041","volume":"23","author":"LJ Craggs","year":"2013","unstructured":"Craggs LJ, Hagel C, Kuhlenbaeumer G, Borjesson-Hanson A, Andersen O, Viitanen M, Kalimo H, McLean CA, Slade JY, Hall RAet al et al (2013) Quantitative vascular pathology and phenotyping familial and sporadic cerebral small vessel diseases. Brain Pathol 23:547\u2013557. https:\/\/doi.org\/10.1111\/bpa.12041","journal-title":"Brain Pathol"},{"key":"1737_CR8","doi-asserted-by":"publisher","first-page":"fcac129","DOI":"10.1093\/braincomms\/fcac129","volume":"4","author":"J Delgado","year":"2022","unstructured":"Delgado J, Masoli J, Hase Y, Akinyemi R, Ballard C, Kalaria RN, Allan LM (2022) Trajectories of cognitive change following stroke: stepwise decline towards dementia in the elderly. Brain Commun 4:fcac129. https:\/\/doi.org\/10.1093\/braincomms\/fcac129","journal-title":"Brain Commun"},{"key":"1737_CR9","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1212\/WNL.0b013e31824e8e7f","volume":"78","author":"V Deramecourt","year":"2012","unstructured":"Deramecourt V, Slade JY, Oakley AE, Perry RH, Ince PG, Maurage CA, Kalaria RN (2012) Staging and natural history of cerebrovascular pathology in dementia. Neurology 78:1043\u20131050. https:\/\/doi.org\/10.1212\/WNL.0b013e31824e8e7f","journal-title":"Neurology"},{"key":"1737_CR10","doi-asserted-by":"publisher","unstructured":"Ding R, Hase Y, Ameen-Ali KE, Ndung\u2019u M, Stevenson W, Barsby J, Gourlay R, Akinyemi T, Akinyemi R, Uemura MT et al (2020) Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer\u2019s disease. Brain Pathol 30:1087\u20131101 https:\/\/doi.org\/10.1111\/bpa.12888","DOI":"10.1111\/bpa.12888"},{"key":"1737_CR11","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s40478-021-01230-6","volume":"9","author":"R Ding","year":"2021","unstructured":"Ding R, Hase Y, Burke M, Foster V, Stevenson W, Polvikoski T, Kalaria RN (2021) Loss with ageing but preservation of frontal cortical capillary pericytes in post-stroke dementia, vascular dementia and Alzheimer\u2019s disease. Acta Neuropathol Commun 9:130. https:\/\/doi.org\/10.1186\/s40478-021-01230-6","journal-title":"Acta Neuropathol Commun"},{"key":"1737_CR12","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1093\/brain\/awv407","volume":"139","author":"E Duzel","year":"2016","unstructured":"Duzel E, van Praag H, Sendtner M (2016) Can physical exercise in old age improve memory and hippocampal function? Brain 139:662\u2013673. https:\/\/doi.org\/10.1093\/brain\/awv407","journal-title":"Brain"},{"key":"1737_CR13","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1016\/j.neurobiolaging.2006.07.009","volume":"28","author":"MJ Firbank","year":"2007","unstructured":"Firbank MJ, Burton EJ, Barber R, Stephens S, Kenny RA, Ballard C, Kalaria RN, O\u2019Brien JT (2007) Medial temporal atrophy rather than white matter hyperintensities predict cognitive decline in stroke survivors. Neurobiol Aging 28:1664\u20131669. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2006.07.009","journal-title":"Neurobiol Aging"},{"key":"1737_CR14","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1212\/WNL.0b013e318217e76a","volume":"76","author":"MJ Firbank","year":"2011","unstructured":"Firbank MJ, He J, Blamire AM, Singh B, Danson P, Kalaria RN, O\u2019Brien JT (2011) Cerebral blood flow by arterial spin labeling in poststroke dementia. Neurology 76:1478\u20131484. https:\/\/doi.org\/10.1212\/WNL.0b013e318217e76a","journal-title":"Neurology"},{"key":"1737_CR15","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1136\/jnnp-2011-300873","volume":"83","author":"MJ Firbank","year":"2012","unstructured":"Firbank MJ, Allan LM, Burton EJ, Barber R, O\u2019Brien JT, Kalaria RN (2012) Neuroimaging predictors of death and dementia in a cohort of older stroke survivors. J Neurol Neurosurg Psychiatry 83:263\u2013267. https:\/\/doi.org\/10.1136\/jnnp-2011-300873","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1737_CR16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1038\/nrneurol.2012.27","volume":"8","author":"M Fotuhi","year":"2012","unstructured":"Fotuhi M, Do D, Jack C (2012) Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol 8:189\u2013202. https:\/\/doi.org\/10.1038\/nrneurol.2012.27","journal-title":"Nat Rev Neurol"},{"key":"1737_CR17","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1161\/strokeaha.111.636498","volume":"43","author":"E Gemmell","year":"2012","unstructured":"Gemmell E, Bosomworth H, Allan L, Hall R, Khundakar A, Oakley AE, Deramecourt V, Polvikoski TM, O\u2019Brien JT, Kalaria RN (2012) Hippocampal neuronal atrophy and cognitive function in delayed poststroke and aging-related dementias. Stroke 43:808\u2013814. https:\/\/doi.org\/10.1161\/strokeaha.111.636498","journal-title":"Stroke"},{"key":"1737_CR18","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1097\/NEN.0000000000000054","volume":"73","author":"E Gemmell","year":"2014","unstructured":"Gemmell E, Tam E, Allan L, Hall R, Khundakar A, Oakley AE, Thomas A, Deramecourt V, Kalaria RN (2014) Neuron volumes in hippocampal subfields in delayed poststroke and aging-related dementias. J Neuropathol Exp Neurol 73:305\u2013311. https:\/\/doi.org\/10.1097\/NEN.0000000000000054","journal-title":"J Neuropathol Exp Neurol"},{"key":"1737_CR19","doi-asserted-by":"publisher","first-page":"110893","DOI":"10.1016\/j.cbpa.2020.110893","volume":"254","author":"S Grubb","year":"2021","unstructured":"Grubb S, Lauritzen M, Aalkjaer C (2021) Brain capillary pericytes and neurovascular coupling. Comp Biochem Physiol Mol Integr Physiol 254:110893. https:\/\/doi.org\/10.1016\/j.cbpa.2020.110893","journal-title":"Comp Biochem Physiol Mol Integr Physiol"},{"key":"1737_CR20","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, O\u2019Farrell FM, Buchan AM, Lauritzen M, Attwell D (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":"1737_CR21","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1177\/0271678X17694904","volume":"38","author":"Y Hase","year":"2018","unstructured":"Hase Y, Craggs L, Hase M, Stevenson W, Slade J, Chen A, Liang D, Ennaceur A, Oakley A, Ihara M al (2018) The effects of environmental enrichment on white matter pathology in a mouse model of chronic cerebral hypoperfusion. J Cereb Blood Flow Metab 38:151\u2013165. https:\/\/doi.org\/10.1177\/0271678X17694904","journal-title":"J Cereb Blood Flow Metab"},{"key":"1737_CR22","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, Platten C, Stevenson W, Craggs LJL, Kalaria RN (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":"1737_CR23","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1111\/nan.12550","volume":"45","author":"Y Hase","year":"2019","unstructured":"Hase Y, Polvikoski TM, Ihara M, Hase M, Zafar R, Stevenson W, Allan LM, Ennaceur A, Horsburgh K, Gallart-Palau Xet al et al (2019) Carotid artery disease in post-stroke survivors and effects of enriched environment on stroke pathology in a mouse model of carotid artery stenosis. Neuropathol Appl Neurobiol 45:681\u2013697. https:\/\/doi.org\/10.1111\/nan.12550","journal-title":"Neuropathol Appl Neurobiol"},{"key":"1737_CR24","doi-asserted-by":"publisher","first-page":"32179","DOI":"10.1038\/srep32179","volume":"6","author":"Y Hattori","year":"2016","unstructured":"Hattori Y, Enmi J, Iguchi S, Saito S, Yamamoto Y, Nagatsuka K, Iida H, Ihara M (2016) Substantial reduction of parenchymal cerebral blood flow in mice with bilateral common carotid artery stenosis. Sci Rep 6:32179. https:\/\/doi.org\/10.1038\/srep32179","journal-title":"Sci Rep"},{"key":"1737_CR25","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1161\/STROKEAHA.122.038263","volume":"54","author":"AC Johnson","year":"2023","unstructured":"Johnson AC (2023) Hippocampal vascular supply and its role in vascular cognitive impairment. Stroke 54:673\u2013685. https:\/\/doi.org\/10.1161\/STROKEAHA.122.038263","journal-title":"Stroke"},{"key":"1737_CR26","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1007\/s00401-016-1571-z","volume":"131","author":"RN Kalaria","year":"2016","unstructured":"Kalaria RN (2016) Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer\u2019s disease. Acta Neuropathol 131:659\u2013685. https:\/\/doi.org\/10.1007\/s00401-016-1571-z","journal-title":"Acta Neuropathol"},{"key":"1737_CR27","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1111\/ene.13243","volume":"24","author":"RN Kalaria","year":"2017","unstructured":"Kalaria RN, Ihara M (2017) Medial temporal lobe atrophy is the norm in cerebrovascular dementias. Eur J Neurol 24:539\u2013540. https:\/\/doi.org\/10.1111\/ene.13243","journal-title":"Eur J Neurol"},{"key":"1737_CR28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jns.2004.09.019","volume":"226","author":"RN Kalaria","year":"2004","unstructured":"Kalaria RN, Kenny RA, Ballard CG, Perry R, Ince P, Polvikoski T (2004) Towards defining the neuropathological substrates of vascular dementia. J Neurol Sci 226:75\u201380. https:\/\/doi.org\/10.1016\/j.jns.2004.09.019","journal-title":"J Neurol Sci"},{"key":"1737_CR29","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/j.cell.2005.01.015","volume":"120","author":"O Lazarov","year":"2005","unstructured":"Lazarov O, Robinson J, Tang YP, Hairston IS, Korade-Mirnics Z, Lee VM, Hersh LB, Sapolsky RM, Mirnics K, Sisodia SS (2005) Environmental enrichment reduces Abeta levels and amyloid deposition in transgenic mice. Cell 120:701\u2013713. https:\/\/doi.org\/10.1016\/j.cell.2005.01.015","journal-title":"Cell"},{"key":"1737_CR30","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.3233\/JAD-190756","volume":"71","author":"A Ledreux","year":"2019","unstructured":"Ledreux A, Hakansson K, Carlsson R, Kidane M, Columbo L, Terjestam Y, Ryan E, Tusch E, Winblad B, Daffner Ket al et al (2019) Differential effects of physical exercise, cognitive training, and mindfulness practice on serum BDNF levels in healthy older adults: a randomized controlled intervention study. J Alzheimer\u2019s Disease: JAD 71:1245\u20131261. https:\/\/doi.org\/10.3233\/JAD-190756","journal-title":"J Alzheimer\u2019s Disease: JAD"},{"key":"1737_CR31","doi-asserted-by":"publisher","first-page":"7095","DOI":"10.1007\/s12035-022-03016-w","volume":"59","author":"AKY Liew","year":"2022","unstructured":"Liew AKY, Teo CH, Soga T (2022) The molecular effects of environmental enrichment on Alzheimer\u2019s disease. Mol Neurobiol 59:7095\u20137118. https:\/\/doi.org\/10.1007\/s12035-022-03016-w","journal-title":"Mol Neurobiol"},{"key":"1737_CR32","unstructured":"Lowe J, Kalaria RN (2015) Dementia. In: Love S PA, Ironside J, Budka H (ed) Greenfield\u2019s Neuropathology 9th Edition edn. CRC Press, City, pp 1001\u20131055"},{"key":"1737_CR33","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1177\/0271678X17690761","volume":"38","author":"JS Miners","year":"2018","unstructured":"Miners JS, Schulz I, Love S (2018) Differing associations between Abeta accumulation, hypoperfusion, blood-brain barrier dysfunction and loss of PDGFRB pericyte marker in the precuneus and parietal white matter in Alzheimer\u2019s disease. J Cereb Blood Flow Metab 38:103\u2013115. https:\/\/doi.org\/10.1177\/0271678X17690761","journal-title":"J Cereb Blood Flow Metab"},{"key":"1737_CR34","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, Toga AW, Jacobs RE, Liu CY, Amezcua Let al 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":"1737_CR35","doi-asserted-by":"publisher","unstructured":"Montagne A, Nikolakopoulou AM, Zhao Z, Sagare AP, Si G, Lazic D, Barnes SR, Daianu M, Ramanathan A, Go A et al (2018) Pericyte degeneration causes white matter dysfunction in the mouse central nervous system. Nat Med 24:326\u2013337 https:\/\/doi.org\/10.1038\/nm.4482","DOI":"10.1038\/nm.4482"},{"key":"1737_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-011-0910-3","volume":"123","author":"TJ Montine","year":"2012","unstructured":"Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SSet al et al (2012) National Institute on Aging-Alzheimer\u2019s Association guidelines for the neuropathologic assessment of Alzheimer\u2019s disease: a practical approach. Acta Neuropathol 123:1\u201311. https:\/\/doi.org\/10.1007\/s00401-011-0910-3","journal-title":"Acta Neuropathol"},{"key":"1737_CR37","doi-asserted-by":"publisher","unstructured":"Nation DA, Sweeney MD, Montagne A, Sagare AP, D\u2019Orazio LM, Pachicano M, Sepehrband F, Nelson AR, Buennagel DP Harrington MG (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","DOI":"10.1038\/s41591-018-0297-y"},{"key":"1737_CR38","doi-asserted-by":"publisher","first-page":"5297","DOI":"10.1093\/cercor\/bhac418","volume":"33","author":"JA Palmer","year":"2023","unstructured":"Palmer JA, Morris JK, Billinger SA, Lepping RJ, Martin L, Green Z, Vidoni ED (2023) Hippocampal blood flow rapidly and preferentially increases after a bout of moderate-intensity exercise in older adults with poor cerebrovascular health. Cereb Cortex 33:5297\u20135306. https:\/\/doi.org\/10.1093\/cercor\/bhac418","journal-title":"Cereb Cortex"},{"key":"1737_CR39","doi-asserted-by":"publisher","unstructured":"Pandey K, Bessieres B, Sheng SL, Taranda J, Osten P, Sandovici I, Constancia M, Alberini CM (2023) Neuronal activity drives IGF2 expression from pericytes to form long-term memory. Neuron 111:3819\u20133836 e3818 https:\/\/doi.org\/10.1016\/j.neuron.2023.08.030","DOI":"10.1016\/j.neuron.2023.08.030"},{"key":"1737_CR40","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.maturitas.2009.09.010","volume":"64","author":"ST Pendlebury","year":"2009","unstructured":"Pendlebury ST (2009) Stroke-related dementia: rates, risk factors and implications for future research. Maturitas 64:165\u2013171. https:\/\/doi.org\/10.1016\/j.maturitas.2009.09.010","journal-title":"Maturitas"},{"key":"1737_CR41","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1016\/S1474-4422(09)70236-4","volume":"8","author":"ST Pendlebury","year":"2009","unstructured":"Pendlebury ST, Rothwell PM (2009) Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis. Lancet Neurol 8:1006\u20131018. https:\/\/doi.org\/10.1016\/S1474-4422(09)70236-4","journal-title":"Lancet Neurol"},{"key":"1737_CR42","first-page":"1","volume-title":"Newcastle Brain Map\u2019. Neuropsychiatric disorders","author":"RH Perry","year":"1993","unstructured":"Perry RH, Oakley AE (1993) Newcastle Brain Map\u2019. Neuropsychiatric disorders. Wolfe, London, pp 1\u201310"},{"key":"1737_CR43","doi-asserted-by":"publisher","first-page":"1185671","DOI":"10.3389\/fnagi.2023.1185671","volume":"15","author":"JA Santiago","year":"2023","unstructured":"Santiago JA, Potashkin JA (2023) Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases. Front Aging Neurosci 15:1185671. https:\/\/doi.org\/10.3389\/fnagi.2023.1185671","journal-title":"Front Aging Neurosci"},{"key":"1737_CR44","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1136\/jnnp.2008.165902","volume":"82","author":"AI Scher","year":"2011","unstructured":"Scher AI, Xu Y, Korf ES, Hartley SW, Witter MP, Scheltens P, White LR, Thompson PM, Toga AW, Valentino DJet al et al (2011) Hippocampal morphometry in population-based incident Alzheimer\u2019s disease and vascular dementia: the HAAS. J Neurol Neurosurg Psychiatry 82:373\u2013376. https:\/\/doi.org\/10.1136\/jnnp.2008.165902","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"1737_CR45","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid Bet al et al (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676\u2013682. https:\/\/doi.org\/10.1038\/nmeth.2019","journal-title":"Nat Methods"},{"key":"1737_CR46","doi-asserted-by":"publisher","first-page":"2598","DOI":"10.1161\/01.STR.0000143725.19053.60","volume":"35","author":"M Shibata","year":"2004","unstructured":"Shibata M, Ohtani R, Ihara M, Tomimoto H (2004) White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. Stroke 35:2598\u20132603. https:\/\/doi.org\/10.1161\/01.STR.0000143725.19053.60","journal-title":"Stroke"},{"key":"1737_CR47","doi-asserted-by":"publisher","first-page":"2957","DOI":"10.1093\/brain\/aww214","volume":"139","author":"OA Skrobot","year":"2016","unstructured":"Skrobot OA, Attems J, Esiri M, Hortobagyi T, Ironside JW, Kalaria RN, King A, Lammie GA, Mann D, Neal Jet al et al (2016) Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. Brain 139:2957\u20132969. https:\/\/doi.org\/10.1093\/brain\/aww214","journal-title":"Brain"},{"key":"1737_CR48","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.expneurol.2017.10.023","volume":"300","author":"M Tachibana","year":"2018","unstructured":"Tachibana M, Yamazaki Y, Liu CC, Bu G, Kanekiyo T (2018) Pericyte implantation in the brain enhances cerebral blood flow and reduces amyloid-beta pathology in amyloid model mice. Exp Neurol 300:13\u201321. https:\/\/doi.org\/10.1016\/j.expneurol.2017.10.023","journal-title":"Exp Neurol"},{"key":"1737_CR49","doi-asserted-by":"publisher","unstructured":"Vockert N, Perosa V, Ziegler G, Schreiber F, Priester A, Spallazzi M, Garcia-Garcia B, Aruci M, Mattern H Haghikia A (2021) hippocampal vascularization patterns exert local and distant effects on brain structure but not vascular pathology in old age. Brain Commun 3:fcab127 https:\/\/doi.org\/10.1093\/braincomms\/fcab127","DOI":"10.1093\/braincomms\/fcab127"},{"key":"1737_CR50","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.yexcr.2005.10.019","volume":"312","author":"D von Tell","year":"2006","unstructured":"von Tell D, Armulik A, Betsholtz C (2006) Pericytes and vascular stability. Exp Cell Res 312:623\u2013629. https:\/\/doi.org\/10.1016\/j.yexcr.2005.10.019","journal-title":"Exp Cell Res"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-024-01737-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40478-024-01737-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-024-01737-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,18]],"date-time":"2024-02-18T18:10:17Z","timestamp":1708279817000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-024-01737-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1737"],"URL":"https:\/\/doi.org\/10.1186\/s40478-024-01737-8","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]},"assertion":[{"value":"8 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approvals were granted by local research ethics committees of the Newcastle upon Tyne Foundation Hospitals Trust. Permission for use of brains for post-mortem research was also granted by consent from next-of-kin or family. All the brain tissues were retained in and obtained from the Newcastle Brain Tissue Resource.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors have no disclosures or conflicts of interest in relation to this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"29"}}