Enhanced Expression of microRNA-1273g-3p Contributes to Alzheimer's Disease Pathogenesis by Regulating the Expression of Mitochondrial Genes

Alzheimer's disease (AD) is the most common form of dementia in the elderly population, but its underlying cause has not been fully elucidated. Recent studies have shown that microRNAs (miRNAs) play important roles in regulating the expression levels of genes associated with AD development. In this study, we analyzed miRNAs in plasma and cerebrospinal fluid (CSF) from AD patients and cognitively normal (including amyloid positive) individuals. miR-1273g-3p was identified as an AD-associated miRNA and found to be elevated in the CSF of early-stage AD patients. The overexpression of miR-1273g-3p enhanced amyloid beta (A beta) production by inducing oxidative stress and mitochondrial impairments in AD model cell lines. A biotin-streptavidin pull-down assay demonstrated that miR-1273g-3p primarily interacts with mitochondrial genes, and that their expression is downregulated by miR-1273g-3p. In particular, the miR-1273g-3p-target gene TIMM13 showed reduced expression in brain tissues from human AD patients. These results suggest that miR-1273g-3p expression in an early stage of AD notably contributes to A beta production and mitochondrial impairments. Thus, miR-1273g-3p might be a biomarker for early diagnosis of AD and a potential therapeutic target to prevent AD progression.

Automated summary

The research identified miR-1273g-3p as an AD-associated miRNA that is elevated in the CSF of early-stage AD patients and enhances Aβ production and mitochondrial impairments. Through a biotin-streptavidin pull-down assay, it was demonstrated that miR-1273g-3p primarily interacts with mitochondrial genes, leading to their downregulation. Target gene analysis showed reduced expression of TIMM13 in brain tissues from human AD patients, indicating that miR-1273g-3p plays a role in early AD pathogenesis.