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 β-protein (Aβ) deposits within vessel walls. In addition to arteries and veins capillaries can also be affected. Aβ deposition into the capillary wall is, thereby, known as capillary CAA (capCAA) and strongly associated with the apolipoprotein E APOEε4 allele as a risk factor. Aβ deposits along the pericapillary glia limitans are described as pericapillary Aβ (pericapAβ: synonymous with pericapillary CAA in other studies). Here, we studied the relationship between pericapAβ and capCAA in 58 human autopsy cases. Although pericapAβ 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 pericapAβ lacking capCAA and vice versa. Moreover, single capillaries show either both pathologies or pericapAβ or capCAA only. There was no local association between these pathologies when analyzing multiple capillaries in each given case. Moreover, pericapAβ predominantly exhibited Aβ(42) whereas capCAA contained both Aβ(42) and Aβ(40). These differences as well as differences in the related astroglial reaction indicate that pericapAβ and capCAA are not directly linked. PericapAβ appears to represent initial Aβ accumulation along the glia limitans that is involved in the perivascular drainage of apoE and Aβ regardless of the APOE genotype whereas capCAA could be explained by a limited transendothelial clearance of apoE4-Aβ complexes compared to apoE2/3-Aβ complexes.
Attems
Johannes
J
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Yamaguchi
Haruyasu
H
Saido
Takaomi C
TC
Thal
Dietmar Rudolf
DR
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002196:Capillaries / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications / Q000473:pathology*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4