Review

Acta Neuropathologica

, Volume 110, Issue 4, pp 345-359

Sporadic cerebral amyloid angiopathy: pathology, clinical implications, and possible pathomechanisms

  • Johannes AttemsAffiliated withPathologic Institute, Otto Wagner Hospital Email author 

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Abstract

Cerebral amyloid angiopathy (CAA) was observed for the first time nearly 100 years ago and systematically described in 1938. It is a common finding in elderly individuals, defined by β-amyloid peptide (Aβ) depositions in cerebral blood vessels, and associated with Alzheimer’s disease (AD). A variety of genetic mutations cause hereditary forms of CAA; in this review, however, only the sporadic variant of CAA is considered. In CAA, Aβ depositions primarily occur in the abluminal portion of the tunica media, and with increasing severity all layers of the blood vessel wall are infiltrated and an additional spread of Aβ into the surrounding neuropil may be seen (i.e., dyshoric changes). CAA is most pronounced in the occipital lobe and its distribution is usually patchy. The relationship between CAA and AD is poorly understood; however, low positive correlations between the severity of both CAA and AD pathology have been observed. CAA is a frequent cause of (warfarin-associated) intracerebral hemorrhage, and the diagnosis of probable CAA-related hemorrhage can be made during life with high accuracy. Both APOE-ε4 and APOE-ε2 are risk factors for CAA, while only APOE-ε2 increases the risk for hemorrhage in CAA. Although the role of CAA as an independent risk factor for cognitive decline is unclear, severe CAA is likely to lower the threshold for clinically overt dementia in neurodegenerative diseases. As for the origin of Aβ in CAA, it may be both produced by smooth muscle cells (vessel wall) and derived from neurons in the course of perivascular drainage.

Keywords

Cerebral amyloid angiopathy Alzheimer’s disease APOE genotype Cerebral hemorrhage Dementia