Cerebral Amyloid Angiopathy in Neurodegenerative Disease

Cerebral amyloid angiopathy (CAA) denotes the deposition of amyloid-β peptides within the walls of leptomeningeal and cortical blood vessels. It frequently co-occurs with Alzheimer’s disease and other neurodegenerative conditions, exacerbating microvascular dysfunction, haemorrhagic risk and cognitive decline. The accumulation of amyloid-β in vessel walls reflects an age-related failure of perivascular clearance pathways, including basement membrane–driven drainage and glymphatic flow, compounded by arterial stiffening and blood–brain barrier breakdown. CAA promotes focal hypoperfusion, microbleeds and neuroinflammation, thereby accelerating synaptic loss and tau pathology. Recognition of CAA’s global importance has spurred advances in non-invasive imaging, fluid biomarkers and stratification strategies for immunotherapy, highlighting its role both as a diagnostic marker and as a therapeutic target in the broader landscape of dementia and cerebrovascular disease.

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Cerebral Amyloid Angiopathy in Neurodegenerative Disease publication trend

The graph below shows the total number of articles in cerebral amyloid angiopathy in neurodegenerative disease across all publications each year (not limited to Nature Index journals).

Technical terms

Cerebral amyloid angiopathy (CAA): Deposition of amyloid-β peptides in the walls of cortical and leptomeningeal vessels, leading to vascular fragility and microbleeds.

Amyloid-β (Aβ): Peptides derived from amyloid precursor protein that aggregate into insoluble fibrils in plaques and vessel walls.

Neurofibrillary tangles: Intracellular aggregates of hyperphosphorylated tau protein associated with synaptic dysfunction and neuron loss.

Perivascular drainage: Clearance pathway by which interstitial fluid and solutes, including Aβ, are removed along basement membranes of cerebral vessels.

Blood–brain barrier (BBB): Selective endothelial interface that regulates molecular exchange between blood and brain parenchyma.

References

1. Brain vasculature accumulates tau and is spatially related to tau tangle pathology in Alzheimer’s disease. Acta Neuropathologica (2024).
2. Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice. Environmental Health Perspectives (2024).
3. Prevalence, distribution, and severity of cerebral amyloid angiopathy differ between Lewy body diseases and Alzheimer’s disease. Acta Neuropathologica Communications (2024).
4. The Cerebrovascular Basement Membrane: Role in the Clearance of β-amyloid and Cerebral Amyloid Angiopathy. Frontiers in Aging Neuroscience (2014).
5. Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease. Alzheimer's Research & Therapy (2009).