{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:24:10Z","timestamp":1787117050136,"version":"build-2736575974"},"reference-count":172,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017506","name":"Alzheimer\u2019s Society","doi-asserted-by":"crossref","award":["8370651\u2013606"],"award-info":[{"award-number":["8370651\u2013606"]}],"id":[{"id":"10.13039\/501100017506","id-type":"DOI","asserted-by":"crossref"}]},{"award":["8370651\u2013606"],"award-info":[{"award-number":["8370651\u2013606"]}],"id":[{"id":"https:\/\/ror.org\/0472gwq90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The pathological deposition of amyloid-\u03b2 (A\u03b2) in the walls of cerebral blood vessels as cerebral amyloid angiopathy (CAA) is a key feature of Alzheimer\u2019s disease (AD) and is linked to impaired clearance of A\u03b2 via intramural periarterial drainage (IPAD). The spontaneous contractions of cerebral smooth muscle cells (SMCs) are thought to drive IPAD, but the relationship between vascular aging and A\u03b2 accumulation remains unclear. We propose a unified framework centered on cerebral intramural cells (CICs), including arterial SMCs, specialized pericyte subtypes, as mediators of vascular dysfunction and neurodegeneration. We integrate current evidence from studies of cerebral small vessel disease, blood\u2013brain barrier (BBB) dysfunction, pericyte biology, vascular aging, cerebral perfusion, and IPAD. CICs regulate vasomotion, capillary flow, BBB integrity, and IPAD. Their dysfunction impairs perfusion and protein clearance, increasing vulnerability in white matter and the hippocampus. These vascular alterations interact with amyloid and inflammatory processes, contributing to synaptic dysfunction, network disconnection, and neurodegeneration. CICs represent potential therapeutic targets. A CIC-centered framework may help explain the links between vascular dysfunction, impaired A\u03b2 clearance, and neurodegeneration in AD and CAA.<\/jats:p>","DOI":"10.3390\/ijms27167353","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:35:08Z","timestamp":1786984508000},"page":"7353","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-3749","authenticated-orcid":false,"given":"Eliza-Mihaela","family":"Arb\u0103na\u0219i","sequence":"first","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Centre for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"British-Romanian Academic Institute of Neuroscience (BRAIN), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1664-8130","authenticated-orcid":false,"given":"Emil-Marian","family":"Arb\u0103na\u0219i","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Centre for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Department of Vascular Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor-Gabriel","family":"Boghi\u021boiu","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie Ada","family":"C\u0103rare","sequence":"additional","affiliation":[{"name":"University Hospital Southampton, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan Andrei","family":"Cordo\u0219","sequence":"additional","affiliation":[{"name":"Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kawthar","family":"Braysh","sequence":"additional","affiliation":[{"name":"Dasman Diabetes Institute, Kuwait City 15462, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoleta","family":"Suciu","sequence":"additional","affiliation":[{"name":"European and Research Projects Department, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Chinezu","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Department of Histology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-4977","authenticated-orcid":false,"given":"Doina Ramona","family":"Manu","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-985X","authenticated-orcid":false,"given":"Axel","family":"Montagne","sequence":"additional","affiliation":[{"name":"Institute for Neuroscience and Cardiovascular Research (INCR), Chancellor\u2019s Building, The University of Edinburgh, Little France Crescent, Edinburgh EH16 4SB, UK"},{"name":"Centre for Clinical Brain Sciences (CCBS), School of Clinical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH16 4SB, UK"},{"name":"UK Dementia Research Institute (UK DRI), University of Edinburgh, Edinburgh EH16 4SB, UK"},{"name":"British Heart Foundation\u2013UK Dementia Research Institute (BHF-UK DRI) Centre for Vascular Dementia Research (CVDR), The University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Dewing","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Russu","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Department of Vascular Surgery, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Clinic of Vascular Surgery, Mures County Emergency Hospital, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-524X","authenticated-orcid":false,"given":"Claudia-Violeta","family":"B\u0103nescu","sequence":"additional","affiliation":[{"name":"Centre for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Department of Genetics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6467-6275","authenticated-orcid":false,"given":"Septimiu-Toader","family":"Void\u0103zan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-Octavia","family":"C\u0103rare","sequence":"additional","affiliation":[{"name":"British-Romanian Academic Institute of Neuroscience (BRAIN), George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK"},{"name":"Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrn1387","article-title":"Neurovascular Regulation in the Normal Brain and in Alzheimer\u2019s Disease","volume":"5","author":"Iadecola","year":"2004","journal-title":"Nat. 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