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Cerebral Amyloid Angiopathy: A Common Cause of Cerebral Hemorrhage

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Abstract:

Amyloid is a term used to describe protein deposits with circumscript physical characteristics: β-pleated sheet configuration, apple green birefringence under polarized light after Congo red staining, fibrillary structure and high insolubility. Cerebral amyloid angiopathy (CAA) defines a clinicopathological phenomenon characterized by amyloid deposition in the walls of leptomeningeal and cortical arteries, arterioles, and, less often capillaries and veins of the central nervous system. CAAs are currently classified according to the protein deposited including amyloid β peptide (Aβ), cystatin C (ACys C), prion protein (PrPSc), ABri/ADan, transthyretin (ATTR), and gelsolin (AGel). Most often amyloid deposition occurs in sporadic forms. In less common hereditary forms, a mutated variant protein or precursor protein is abnormally metabolized by proteolytic pathways in consequence of specific gene mutations, and accumulates as amyloid. The spectrum of clinical phenotypes associated with CAA-related vasculopathic changes includes both ischemic and hemorrhagic presentations, primary intracerebral hemorrhage (PICH) being probably the most well-recognized. However, in spite of accumulating data and recent progress in understanding the pathogenesis of CAA-related hemorrhage, the exact mechanisms leading to vessel rupture in these cases are yet to be established. This represents, at present, a major limitation to the identification of reliable biomarkers and the development of disease-specific treatment options. The present paper summarizes epidemiologic and clinical aspects of CAA, and highlights the presumed pathomechanisms of amyloid deposition in both sporadic and hereditary forms.

Keywords: Cerebral amyloid angiopathy; hereditary cerebral hemorrhage with amyloidosis; intracerebral hemorrhage; β amyloid peptide

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709788682047

Affiliations: Neurology Clinic, University of Brescia, P.le Spedali Civili, 1, 25125 Brescia, Italy.

Publication date: July 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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