Abstract
Alzheimer's disease (AD) arises from converging neurodegeneration and neuroinflammation, yet post-transcriptional mechanisms linking these processes remain poorly defined. Hsa-miR-132-3p, a neuron-enriched microRNA consistently downregulated in AD, has emerged as a candidate integrator of synaptic plasticity and innate immune signaling. Targets of hsa-miR-132-3p were collected from five repositories (miRTarBase v10.0, DIANA-TarBase v9.0, ENCORI v3.0, miRWalk v3.0, miRDB v6.0) and integrated using multiMiR. Functional annotation used ShinyGO v0.81 (KEGG, GO-BP), with immune enrichment via MSigDB Hallmark, ImmPort, and InnateDB. High-confidence targets were defined by overlap with TargetScan conserved predictions and MalaCards AD genes. PPI networks were built with STRING v12.0/MCODE, and transcriptomic validation used GSE5281 hippocampal microarray data. Integration of five repositories identified 5429 non-redundant candidate targets, with significant enrichment in prefrontal cortex and CD33 + myeloid cell signatures (adjusted p < 0.05). Immune analyses highlighted TNFα/NF-κB, IL-6/JAK-STAT3, and interferon signaling overrepresentation. Intersection with TargetScan conserved predictions and MalaCards prioritized a 14-gene module (GSK3B, MAPK1, MAPK3, EP300, FOXO3, PIK3CA, PPP3CA, MAPT, EGR1, NR4A2, SLC30A6, ADCYAP1, SLC6A3, SV2A) defined by the convergence of experimentally supported target annotations, conserved TargetScan predictions, and AD-associated gene annotations. PPI mapping identified MAPK1, MAPK3, EP300, MAPT, and EGR1 as a central interaction module associated with inflammatory signaling and tau-associated processes. Hippocampal transcriptomic analysis provided exploratory evidence of overlap between candidate hsa-miR-132-3p targets and AD-associated differentially expressed genes (KDM4B,CBX3 and MORF4L2). This analysis nominates hsa-miR-132-3p as a candidate post-transcriptional regulator potentially linking neuronal stress, tau pathology, and innate immune signaling in AD. The 14-gene module provides a hypothesis-generating framework for cell-type-resolved experimental validation.