A distinct brain beta amyloid signature in cerebral amyloid angiopathy compared to Alzheimer's disease

Cerebral amyloid angiopathy (CAA) is a type of vascular disease present in more than 50% of demented elderly and more than 80% of Alzheimer's disease (AD) patients. Both CAA and AD are characterized by extracellular A beta deposits with the distinction that CAA has vascular deposits while AD has amyloid plaques. In this study, we used immunoprecipitation (IP) in combination with mass spectrometry (MS) to test the hypothesis that the A beta peptide pattern differs between subjects having All plaque pathology only and subjects with A beta plaque pathology together with CAA pathology. Occipital lobes from 12 AD brains, ranging from no CAA to severe CAA, were extracted using 70% formic acid followed by IP-MS analysis. The A beta peptide pattern differed greatly between subjects with no CAA compared to subjects with CAA. In cases with CAA, the most abundant A beta peptides ended at amino acid 40 including A beta 1-40 (P = .048) and A beta 2-40 (P = .0253) which were significantly increased compared to cases with no CAA. This was in contrast to subjects with no CAA where the most abundant A beta peptides ended at amino acid 42 of which A beta 1-42 (P = .0101) and A beta 2-42 (P = .0051) as well as the pyroglutamate (pGlu)-modified peptides pGlu A beta 3-42 (P = .0177), and pGlu A beta 11-42 (P = .0088) were significantly increased compared to CAA subjects. The results are in line with earlier immunohistochemistry data and show that the molecular composition of the A beta deposits found in blood vessels are different to the parenchymal deposits, suggesting they arise from distinct pathogenic pathways. This information may be useful in the development of pathology-specific biomarkers.