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Updated: Sep 30, 2025
Using Retinal Imaging to Study Dementia
Published on: November 6, 2017
Pathological changes within the cerebral vasculature in Alzheimer's disease: New perspectives
Robert A Fisher1, J Scott Miners1, Seth Love1
1Dementia Research Group, University of Bristol Medical School, Bristol, UK.
Insights
Cerebral small vessel disease and amyloid angiopathy contribute to Alzheimer's disease (AD) pathology and cognitive decline. Vascular dysfunction in AD impairs Aβ clearance and promotes amyloid production, highlighting a bi-directional relationship.
Area of Science:
- Neurology
- Pathology
- Vascular Biology
Background:
- Cerebrovascular disease is central to vascular dementia (VaD).
- Structural and functional changes in cerebral vasculature contribute to Alzheimer's disease (AD) pathology and cognitive decline.
- Key vascular pathologies in AD include cerebral amyloid angiopathy and non-amyloid small vessel disease.
Purpose of the Study:
- To review the contribution of cerebrovascular changes to AD pathogenesis.
- To explore the impact of vascular abnormalities on amyloid-beta (Aβ) clearance and production.
- To discuss the bi-directional relationship between vascular dysfunction and Aβ accumulation in AD.
Main Methods:
- Literature review focusing on cerebrovascular contributions to AD.
- Analysis of changes in vessel density, maintenance, and remodeling.
- Examination of neurovascular unit cell function and blood-brain barrier (BBB) integrity.
- Review of Aβ clearance mechanisms (IPAD, BBB transport) and neurovascular coupling.
- Discussion of methodological advances in transcriptomics and imaging.
Main Results:
- Vascular changes, including alterations to the cerebrovascular basement membrane, impact AD pathogenesis.
- Abnormalities in endothelial cells and pericytes, alongside BBB impairment, are critical.
- Impaired Aβ clearance and reduced cerebral blood flow exacerbate amyloidogenic processing.
- Aβ peptides possess vasoactive properties, suggesting a feedback loop with vascular dysfunction.
- Retinal vascular assessment offers potential for early AD detection.
Conclusions:
- Cerebrovascular dysfunction is a significant driver of AD pathology and cognitive impairment.
- The interplay between vascular health and amyloid pathology is bi-directional and complex.
- Novel transcriptomic and imaging techniques are advancing our understanding of vascular roles in AD.
- Non-invasive retinal imaging may provide early diagnostic insights into AD-related vascular changes.
Abstract:
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.
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