Capillary CAA and perivascular Aβ-deposition: Two distinct features of Alzheimer's disease pathology

Cerebral amyloid angiopathy (CAA) is frequently seen in Alzheimer's disease (AD) cases and represents one of its histopathological hallmarks. CAA is characterized by amyloid beta-protein (A beta) deposits within vessel walls. In addition to arteries and veins capillaries can also be affected. A beta deposition into the capillary wall is, thereby, known as capillary CAA (capCAA) and strongly associated with the apolipoprotein E APOE epsilon 4 allele as a risk factor. A beta deposits along the pericapillary glia limitans are described as pericapillary A beta (pericapA beta: synonymous with pericapillary CAA in other studies). Here, we studied the relationship between pericapA beta and capCAA in 58 human autopsy cases. Although pericapA beta and capCAA were more frequently found in AD cases compared to controls and although they exhibited a correlation to one another, detailed analysis revealed that there is a significant number of cases with pericapA beta lacking capCAA and vice versa. Moreover, single capillaries show either both pathologies or pericapA beta or capCAA only. There was no local association between these pathologies when analyzing multiple capillaries in each given case. Moreover, pericapA beta predominantly exhibited A beta(42) whereas capCAA contained both A beta(42) and A beta(40). These differences as well as differences in the related astroglial reaction indicate that pericapA beta and capCAA are not directly linked. PericapA beta appears to represent initial A beta accumulation along the glia limitans that is involved in the perivascular drainage of apoE and A beta regardless of the APOE genotype whereas capCAA could be explained by a limited transendothelial clearance of apoE4-A beta complexes compared to apoE2/3-A beta complexes. (C) 2010 Elsevier B.V. All rights reserved.