Pathological changes within the cerebral vasculature in Alzheimer's disease: New perspectives

Robbie A Fisher*, J Scott Miners, Seth Love*

*Corresponding author for this work

Research output: Contribution to journalReview article (Academic Journal)peer-review

36 Citations (Scopus)
162 Downloads (Pure)


Cerebrovascular disease underpins vascular dementia (VaD), but structural and functional changes to the cerebral vasculature contribute to disease pathology and cognitive decline in Alzheimer's disease (AD). In this review, we discuss the contribution of cerebral amyloid angiopathy and non-amyloid small vessel disease in AD, and the accompanying changes to the density, maintenance and remodelling of vessels (including alterations to the composition and function of the cerebrovascular basement membrane). We consider how abnormalities of the constituent cells of the neurovascular unit - particularly of endothelial cells and pericytes - and impairment of the blood-brain barrier (BBB) impact on the pathogenesis of AD. We also discuss how changes to the cerebral vasculature are likely to impair Aβ clearance - both intra-periarteriolar drainage (IPAD) and transport of Aβ peptides across the BBB, and how impaired neurovascular coupling and reduced blood flow in relation to metabolic demand increase amyloidogenic processing of APP and the production of Aβ. We review the vasoactive properties of Aβ peptides themselves, and the probable bi-directional relationship between vascular dysfunction and Aβ accumulation in AD. Lastly, we discuss recent methodological advances in transcriptomics and imaging that have provided novel insights into vascular changes in AD, and recent advances in assessment of the retina that allow in vivo detection of vascular changes in the early stages of AD.

Original languageEnglish
Article numbere13061
JournalBrain Pathology
Issue number6
Early online date14 Mar 2022
Publication statusPublished - 28 Oct 2022

Bibliographical note

Funding Information:
Some of the studies described in this review were supported by funding from Alzheimer's Research UK (ARUK‐SRF‐2019A‐001), Alzheimer's Society (UK)

Publisher Copyright:
© 2022 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Structured keywords

  • Dementia Research Group


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