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Background and Purpose— Cerebral small vessel disease (SVD) is a frequent pathology in aging and contributor to the development of dementia. Plasma Aβ (amyloid β) levels may be useful as early biomarker, but the role of plasma Aβ in SVD remains to be elucidated. We investigated the association of plasma Aβ levels with severity and progression of SVD markers. Methods— We studied 487 participants from the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort) of whom 258 participants underwent 3 MRI assessments during 9 years. We determined baseline plasma Aβ38, Aβ40, and Aβ42 levels using ELISAs. We longitudinally assessed volume of white matter hyperintensities semiautomatically and manually rated lacunes and microbleeds. We analyzed associations between plasma Aβ and SVD markers by ANCOVA adjusted for age, sex, and hypertension. Results— Cross-sectionally, plasma Aβ40 levels were elevated in participants with microbleeds (mean, 205.4 versus 186.4 pg/mL;P &lt;0.01) and lacunes (mean, 194.8 versus 181.2 pg/mL;P &lt;0.05). Both Aβ38 and Aβ40 were elevated in participants with severe white matter hyperintensities (Aβ38, 25.3 versus 22.7 pg/mL;P &lt;0.01; Aβ40, 201.8 versus 183.3 pg/mL;P &lt;0.05). Longitudinally, plasma Aβ40 levels were elevated in participants with white matter hyperintensity progression (mean, 194.6 versus 182.9 pg/mL;P &lt;0.05). Both Aβ38 and Aβ40 were elevated in participants with incident lacunes (Aβ38, 24.5 versus 22.5 pg/mL;P &lt;0.05; Aβ40, 194.9 versus 181.2 pg/mL;P &lt;0.01) and Aβ42 in participants with incident microbleeds (62.8 versus 60.4 pg/mL;P &lt;0.05).Conclusions— Plasma Aβ levels are associated with both presence and progression of SVD markers, suggesting that Aβ pathology might contribute to the development and progression of SVD. Plasma Aβ levels might thereby serve as inexpensive and noninvasive measure for identifying individuals with increased risk for progression of SVD.

Plasma Aβ (Amyloid-β) Levels and Severity and Progression of Small Vessel Disease