Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Aβ isoforms, i.e., Aβ1-40 and Aβ 1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Aβ levels including novel Aβ 1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementia Objective: To examine the association of plasma Aβ levels (i.e., Aβ1-38, Aβ 1-40, and Aβ 1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting. Methods: We analyzed plasma A-1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Aβ levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta-Analysis with fixed effects. Results: Higher levels of plasma Aβ 1-38, Aβ 1-40, Aβ 1-42, and Aβ 1-40/ Aβ 1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels ofAβ1-40 andAβ 1-40/ Aβ1-42 were significantly associated with largerWMH volumes. With regard to cognition, a higher level of Aβ 1-38 Aβ 1-40 and Aβ 1-40/ Aβ 1-42 was related to worse performance on cognitive test specifically in memory domain. Conclusion: Higher plasma levels of Aβ levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Aβ levels thus mark the presence of vascular brain pathology.

Additional Metadata
Keywords Cerebral small vessel disease, cognition, magnetic resonance imaging, plasma amyloid-β levels, Population-based
Persistent URL dx.doi.org/10.3233/JAD-170458, hdl.handle.net/1765/102515
Journal Journal of Alzheimer's Disease
Citation
Hilal, S, Akoudad, S, van Duijn, C.M, Niessen, W.J, Verbeek, M.M, Vanderstichele, H.M.J, … Vernooij, M.W. (2017). Plasma Amyloid-β Levels, Cerebral Small Vessel Disease, and Cognition: The Rotterdam Study. Journal of Alzheimer's Disease, 60(3), 977–987. doi:10.3233/JAD-170458