Abstract
A synaptic protein, Neuronal Pentraxin 2 (NPTX2), has emerged as a pivotal biomarker for Alzheimer's dementia (AD). We identified candidate miRNAs targeting NPTX2 and performed association and mediation analyses using multi-omics data (N = 702). Among 44 candidate miRNAs, miR-133b was significantly associated with AD and Braak positivity. Higher miR-133b expression was also associated with higher NPTX2 gene expression and better cognition. Mediation analysis showed that miR-133b partially influences AD and cognition through the NPTX2 protein. Our integrated approach suggests a potential role of miR-133b in synaptic integrity and offers new insights into AD pathogenesis.