title: Two types of sporadic cerebral amyloid angiopathy.
abstract: Cerebral amyloid angiopathy (CAA) is a type of beta-amyloidosis that occurs in leptomeningeal and cortical vessels of the elderly. In a sample of 41 CAA cases including 16 Alzheimer disease (AD) cases and 28 controls, we show that 2 types of sporadic CAA exist: The first type is characterized by immunohistochemically detectable amyloid beta-protein (Abeta) in cortical capillaries, leptomeningeal and cortical arteries, arterioles, veins, and venules. It is referred to here as CAA-Type 1. The second type of CAA also exhibits immunohistochemically detectable Abeta deposits in leptomeningeal and cortical vessels, with the exception of cortical capillaries. This type is termed CAA-Type 2. In cases with CAA-Type 1, the frequency of the apolipoprotein E (ApoE) epsilon4 allele is more than 4 times greater than in CAA-Type 2 cases and in controls. CAA-Type 2 cases have a higher epsilon2 allele frequency than CAA-Type 1 cases and controls. The ratio of CAA-Type 2 to CAA-Type 1 cases does not shift significantly with respect to the severity of AD-related beta-amyloidosis, with respect to degrees of CAA-severity, or with increasing age. Therefore, CAA-Type 1 is unlikely to be the late stage of CAA-Type 2; rather, they represent 2 different entities. Since both the ApoE epsilon2 and the epsilon4 allele are known to be risk factors for CAA, we can assign the risk factor ApoE epsilon4 to a distinct morphological type of CAA. The ApoE epsilon4 allele constitutes a risk factor for CAA-Type 1 and, as such, for neuropil-associated dyshoric vascular Abeta deposition in capillaries, whereas the e2 allele does not. CAA-Type 2 is not associated with the epsilon4 allele as a risk factor but shows a higher epsilon2 allele frequency than CAA-Type 1 cases and controls in our sample.
authors.affiliation: Department of Clinical Neuroanatomy, J.W. Goethe University, Frankfurt am Main, Germany.
authors.forename: Dietmar Rudolf
authors.initials: DR
authors.lastname: Thal
authors.forename: Estifanos
authors.initials: E
authors.lastname: Ghebremedhin
authors.forename: Udo
authors.initials: U
authors.lastname: Rüb
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Kelly
authors.initials: K
authors.lastname: Del Tredici
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000150:complications; D001057:Apolipoproteins E / Q000235:genetics; D001808:Blood Vessels / Q000378:metabolism; D001927:Brain Diseases / Q000150:complications; D002196:Capillaries / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000145:classification* / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D002544:Cerebral Infarction / Q000150:complications; D002560:Cerebrovascular Circulation; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012720:Severity of Illness Index
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E