Relative paucity of tau accumulation in the small areas with abundant Aβ42-positive capillary amyloid angiopathy within a given cortical region in the brain of patients with Alzheimer pathology

Cerebral amyloid angiopathy (CAA) is a manifestation of amyloid β-protein (Aβ) accumulation in the elderly as well as in patients with Alzheimer’s disease (AD). Two types of CAA have been noted, based on the type of vasculature in which Aβ is deposited: cerebral capillary amyloid angiopathy (capCAA) and non-capCAA. Non-capCAA is a common form of CAA that consists of Aβ deposited in arteries and arterioles. Recent information on Aβ metabolism in the brain suggests that non-capCAA is associated with Aβ secretion into the cerebrospinal fluid via the perivascular space, whereas capCAA is associated with Aβ removal to blood plasma via the capillary endothelium. Aβ40, a major and relatively soluble Aβ isoform, is deposited predominantly in non-capCAA, and Aβ42, which is insoluble and associated more closely than Aβ40 with AD, is deposited predominantly in capCAA. Studying small areas of microscopic size within a given cortical region, we found an inverse association of capCAA and senile plaques. We also found a relative paucity of tau pathology in the small areas with abundant capCAA compared with the small areas with abundant senile plaques within a cortical region with the same cytoarchitecture. We suppose that both capCAA and senile plaques indicate high Aβ42 in the neuropil but that only Aβ42 in the form of insoluble deposits in senile plaques promotes tau abnormality.