Vascular Contributions to Alzheimer's Disease Pathology

Alzheimer’s disease is increasingly recognised not only as a primary neurodegenerative disorder but also as one intricately linked to cerebrovascular dysfunction. Structural and functional alterations in cerebral vessels—including microbleeds, white matter lesions and small‐vessel disease—compromise blood flow and impair clearance of neurotoxic proteins. Hypoperfusion and blood–brain barrier breakdown foster accumulation of amyloid-β and tau aggregates, triggering neuroinflammation and synaptic loss. Concomitant risk factors such as midlife hypertension, diabetes and obesity exacerbate vascular injury, thereby lowering the threshold for clinical dementia. Cerebral amyloid angiopathy further links vascular amyloid deposits with vessel wall fragility, accelerating cognitive decline. The overlap of vascular pathology and classic Alzheimer hallmarks gives rise to mixed dementia, in which ischaemic lesions and neurodegenerative changes act synergistically. Understanding these interactions opens avenues for prevention and treatment by targeting vascular health, improving cerebral perfusion and enhancing removal of pathogenic proteins.

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Vascular Contributions to Alzheimer's Disease Pathology publication trend

The graph below shows the total number of articles in vascular contributions to alzheimer's disease pathology across all publications each year (not limited to Nature Index journals).

Technical terms

Amyloid-β: A peptide that aggregates into extracellular plaques, central to Alzheimer’s pathology.

Tau aggregates: Abnormally phosphorylated tau proteins that form intracellular neurofibrillary tangles.

Microbleeds: Small focal haemorrhages in the brain indicative of vessel fragility and blood–brain barrier compromise.

Cerebral amyloid angiopathy: Deposition of amyloid-β in vessel walls, leading to vessel stiffness and risk of haemorrhage.

White matter lesions: Areas of demyelination and gliosis visible on MRI, reflecting chronic small vessel ischaemia.

References

1. Interactions between vascular burden and amyloid-β pathology on trajectories of tau accumulation. Brain (2023).
2. Cardiometabolic risk factors and neurodegeneration: a review of the mechanisms underlying diabetes, obesity and hypertension in Alzheimer’s disease. Journal of Neurology Neurosurgery & Psychiatry (2024).
3. The overlap between vascular disease and Alzheimer’s disease - lessons from pathology. BMC Medicine (2014).