Mapping cerebrospinal fluid biomarkers to dementia risk through Mendelian randomization

Cerebrospinal fluid (CSF) biomarkers can directly reflect physiological and pathological changes within the central nervous system, serving as a critical element in the preliminary diagnosis and disease monitoring of central nervous system disorders. Specific CSF biomarker patterns may be associated with different types of dementia. The goal of this analysis is to scrutinize the causal correlation between 338 CSF biomarkers and the danger of 4 dementia categories, namely Alzheimer disease, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies, using Mendelian randomization (MR) analysis. Forward and reverse MR were employed to examine this causal relationship. Inverse variance weighting was used as the primary statistical method, with weighted median, MR-Egger, simple mode, and weighted mode methods as supplementary approaches. Concurrently, scrutiny of horizontal pleiotropy, heterogeneity, and sensitivity was undertaken to substantiate the inferences made from the MR study. We identified 9 positive and 12 negative causal relationships between genetic predisposition to CSF biomarkers and dementia. Notably, a bidirectional causal relationship was found between 3-methoxytyrosine levels and Alzheimer disease. The findings of this MR study support a causal association between CSF biomarkers and the risk of 4 distinct types of dementia.