Abstract
Cerebral small vessel disease (SVD) is a frequent pathology in aging and contributor to the development of dementia. Cerebral amyloid angiopathy (CAA) is one of the potential causes of SVD, characterized by deposition of amyloid β (Aβ) proteins in cerebral blood vessels. Plasma Aβ levels may be useful as an early non-invasive marker of CAA. We investigated the association of plasma Aβ levels with severity and progression of SVD markers in non-demented elderly with SVD. We studied 487 participants from the RUN DMC cohort study of whom 258 participants underwent three MRI assessments over a period of nine years. We determined baseline plasma levels of Aβ38, Aβ40 and Aβ42 peptides using ELISAs. We assessed volume of white matter hyperintensities (WMH) by semi-automatic segmentation, and manually rated lacunes and microbleeds as markers of SVD. We analyzed associations between plasma Aβ and SVD markers by ANCOVA with adjustments for age, sex and hypertension. Plasma Aβ40 levels were elevated in participants with microbleeds (mean 205.4 vs. 186.4 pg/ml; p<0.01), lacunes (mean 194.8 vs. 181.2 pg/ml; p<0.05) and moderate to severe WMH (mean 201.8 vs. 183.3 pg/ml; p<0.05) compared to participants without these SVD markers. High plasma Aβ40 levels were associated with increased risk of incident lacunes and progression of WMH. Elevated plasma Aβ42 levels were associated with incident microbleeds over nine years (p<0.05). Plasma Aβ levels are associated with both presence and progression of neuroimaging markers of SVD. These data suggest that plasma Aβ levels could possibly serve as inexpensive and non-invasive measure for identifying individuals with increased risk for SVD. This study was part of the CAVIA project: Cerebral Amyloid Angiopathy: Vascular Imaging and fluid markers of Amyloid deposition.
Published Version
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