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Relation of plasma β-amyloid, clusterin, and tau with cerebral microbleeds: Framingham Heart Study
José Rafael Romero1,2, Serkalem Demissie3, Alexa Beiser1,2,3
1Department of Neurology, Boston University School of Medicine, Boston, Massachusetts.
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.
Insights
Plasma Aβ1-40 and Tau levels are linked to cerebral microbleeds (CMBs), which are markers of small vessel disease. Further research is needed to confirm their role in predicting neurological injury.
Area of Science:
- Neurology
- Biomarker Discovery
- Cerebrovascular Disease Research
Background:
- Cerebral microbleeds (CMBs) are indicators of cerebral small vessel disease (CSVD), increasing stroke and dementia risk.
- CMBs are classified as deep (hypertensive) or lobar (cerebral amyloid angiopathy).
- Identifying biomarkers for CMBs can aid in early diagnosis and risk stratification.
Purpose of the Study:
- To investigate the association between plasma levels of amyloid-beta (Aβ) peptides (Aβ1-40, Aβ1-42, and their ratio), clusterin, and tau with the presence and location of CMBs.
- To explore the potential of these biomarkers in reflecting underlying angiopathies associated with CMBs.
Main Methods:
- Utilized data from Framingham Heart Study participants free of neurological diseases.
- Employed multivariable logistic regression to analyze the relationship between standardized plasma biomarker levels and CMB presence (overall, lobar, and deep).
Main Results:
- Plasma Aβ1-40 was associated with any CMB and lobar CMB, but not deep CMB.
- Clusterin showed a relationship with mixed CMB.
- Plasma Tau levels were significantly associated with any CMB, lobar CMB, and deep CMB.
Conclusions:
- Plasma Aβ1-40 and Tau show potential as biomarkers associated with CMBs.
- Further investigation is required to validate their role in predicting hemorrhage-prone CSVD and subclinical neuronal injury.