Two Types of Sporadic Cerebral Amyloid Angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is a type of β-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 β-protein (Aβ) 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 Aβ 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) ϵ4 allele is more than 4 times greater than in CAA-Type 2 cases and in controls. CAA-Type 2 cases have a higher ϵ2 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 β-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 ϵ2 and the ϵ4 allele are known to be risk factors for CAA, we can assign the risk factor ApoE ϵ4 to a distinct morphological type of CAA. The ApoE ϵ4 allele constitutes a risk factor for CAA-Type 1 and, as such, for neuropil-associated dyshoric vascular Aβ deposition in capillaries, whereas the ϵ2 allele does not. CAA-Type 2 is not associated with the ϵ4 allele as a risk factor but shows a higher ϵ2 allele frequency than CAA-Type 1 cases and controls in our sample.