Capillary cerebral amyloid angiopathy in Alzheimer's disease: association with allocortical/hippocampal microinfarcts and cognitive decline.

Abstract

Cerebral amyloid angiopathy (CAA) is caused by the deposition of the amyloid β-protein (Aβ) in the wall of cerebral and leptomeningeal blood vessels and is related to Alzheimer's disease (AD). Capillary Aβ deposition is observed in a subset of CAA cases and represents a distinct type of CAA named capillary CAA or CAA type 1. This type of CAA is strongly associated with the presence of the apolipoprotein E ε4 allele. CAA type 1-associated AD cases often exhibit a more severe Aβ plaque pathology but less widespread neurofibrillary tangle (NFT) pathology. The objective of this study was to analyze whether capillary CAA and its effects on cerebral blood flow have an impact on dementia. To address this objective, we performed neuropathological evaluation of 284 autopsy cases of demented and non-demented individuals. We assessed the presence of CAA and its subtypes as well as for that of hemorrhages and infarcts. Capillary CAA and CAA severity were associated with allocortical microinfarcts, comprising the CA1 region of the hippocampus. Allocortical microinfarcts, capillary CAA and CAA severity were, thereby, associated with cognitive decline. In conclusion, allocortical microinfarcts, CAA severity, and the capillary type of CAA were associated with one another and with the development of cognitive decline. Thus, AD cases with CAA type 1 (capillary CAA) appear to develop dementia symptoms not only due to AD-related Aβ plaque and NFT pathology but also due to hippocampal microinfarcts that are associated with CAA type 1 and CAA severity, and that damage a brain region important for memory function.