Relation of Plasma β-amyloid, Clusterin, and Tau with Cerebral Microbleeds: Framingham Heart Study

Objective: Cerebral microbleeds (CMBs) are associated with higher risk of stroke and dementia, predating clinical diagnosis by several years. CMB are considered markers of cerebral small vessel disease (CSVD): hypertensive (deep CMB) and cerebral amyloid angiopathy (lobar CMB). We related plasma β-Amyloid (40, 42 and their ratio), clusterin, and tau levels to CMB to elucidate their role as biomarkers for the angiopathies represented by CMB.

Methods: Dementia, stroke, and other neurological disease-free Framingham Heart Study participants with available CMB and biomarker measurements were included. We related biomarker levels (standardized for analyses) to CMB presence overall and stratified by brain topography (any, lobar, deep), using multivariable logistic regression analyses.

Results: CMB were observed in 208 (5.7%) participants (mean age 57 years, 54% women). After multivariable adjustment, Aβ1-40 was associated with any CMB (OR (95%CI) 1.20 (0.99, 1.45) P = 0.062)) and lobar CMB (OR (95%CI) 1.33 (1.05, 1.68) P = 0.019), but not with deep CMB. Log-Aβ1-42 levels were not associated with CMB overall. Clusterin was related to mixed CMB (1.70 [1.05, 2.74], P = 0.031). Tau levels were associated with any CMB (OR (95%CI) 1.26 (1.07, 1.49) P = 0.006), lobar CMB (OR (95%CI) 1.26 (1.05, 1.52) P = 0.013), and with deep CMB (OR (95% CI) 1.46 (1.13, 1.89) P = 0.004).

Interpretation: We found that plasma Aβ1-40 and Tau are associated with CMB but further studies are needed to confirm their role in hemorrhage prone CSVD represented by CMB and as indicators of ongoing subclinical neuronal injury.