Progression of cerebral amyloid angiopathy: A pathophysiological framework

Abstract

Cerebral amyloid angiopathy, which is defined by cerebrovascular deposition of amyloid , is a common age-related small vessel pathology associated with intracerebral haemorrhage and cognitive impairment. Based on complementary lines of evidence from in vivo studies of individuals with hereditary, sporadic, and iatrogenic forms of cerebral amyloid angiopathy, histopathological analyses of affected brains, and experimental studies in transgenic mouse models, we present a framework and timeline for the progression of cerebral amyloid angiopathy from subclinical pathology to the clinical manifestation of the disease. Key stages that appear to evolve sequentially over two to three decades are (stage one) initial vascular amyloid deposition, (stage two) alteration of cerebrovascular physiology, (stage three) non-haemorrhagic brain injury, and (stage four) appearance of haemorrhagic brain lesions. This timeline of stages and the mechanistic processes that link them have substantial implications for identifying disease-modifying interventions for cerebral amyloid angiopathy and potentially for other cerebral small vessel diseases.

RAS ID

62014

Document Type

Journal Article

Date of Publication

7-1-2023

Volume

22

Issue

7

Funding Information

Dutch CAA Foundation

PubMed ID

37236210

School

School of Medical and Health Sciences

Copyright

subscription content

Publisher

Elsevier

Comments

Koemans, E. A., Chhatwal, J. P., van Veluw, S. J., van Etten, E. S., van Osch, M. J. P., van Walderveen, M. A. A., . . . Greenberg, S. M. (2023). Progression of cerebral amyloid angiopathy: A pathophysiological framework. The Lancet Neurology, 22(7), 632-642. https://doi.org/10.1016/S1474-4422(23)00114-X

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Link to publisher version (DOI)

10.1016/S1474-4422(23)00114-X