Causal inference analysis of the effect of amyloid-β and tau proteins on dementia risk: A Mendelian randomization analysis
Jacob Apibilla Ayembilla, Rachael Osemudiamen Osagie, Adeyemi Timothy Akinade, Oumar Sako, Oluwafunmbi Ebenezer Ogunmiluyi, Olaitan I. AweBackground
The global burden of dementia is escalating due to the aging population. While amyloid and tau biomarkers are central to Alzheimer's disease (AD) pathology, their causal roles across dementia subtypes are not fully understood.
Objective
This study investigated the causal effects of cerebrospinal fluid (CSF) and plasma amyloid, tau, and hyperphosphorylated tau (p-tau) proteins on dementia [AD, frontotemporal dementia (FTD), and vascular dementia (VaD)] risk.
Methods
In this study, we conducted a two-sample Mendelian randomization analysis using genome-wide association study (GWAS) summary statistics. The AD, CSF, and plasma amyloid, tau, and p-tau data were obtained from the GWAS catalog, while those for FTD and VaD were obtained from the FINNGEN database. The inverse variance weighting method, combined with sensitivity analysis, was used to obtain the estimates.
Results
CSF p-tau in individuals with abnormal amyloid and
Conclusions
The findings support the causal roles of tau and amyloid across dementia subtypes, reinforcing the value of biomarker-driven prevention and therapeutic strategies.