Differentially expressed miRNAs in the temporal cortex of Alzheimer’s disease patients and their association to tau pathology

Alzheimer's disease (AD) is a major contributor to dementia in the elderly, characterized by progressive impairments in memory and behaviour. AD is marked by pathological hallmarks: amyloid plaques and neurofibrillary tangles (NFTs). Despite extensive efforts to understand these hallmarks, there is still a lack of efficient therapeutic approaches due to limited knowledge of the fundamental cellular mechanisms underlying the disease. One potential avenue of research involves the investigation of the roles of non-coding RNAs, particularly microRNAs (miRNAs), which bind to the 3' UTRs of target mRNAs to suppress expression. In our study, we analyse the temporal superior T1 isocortex of control and AD patients, identifying differentially expressed miRNAs using next-generation sequencing (NGS). To validate these findings, we utilize an additional technique, RT-qPCR. Our study confirms the previous findings on the dysregulation of miR-129-5p, miR-132-3p, and miR-146b-5p, while also provides insights into the dysregulation of miR-151a-5p and miR-1-3p. Importantly, the expression levels of miR-129-5p, miR-146b-5p, miR-132-3p, and miR-151a-5p are significantly correlated with the neuropathological Braak stages and with biochemically quantified tau phosphorylation levels in brain homogenates. Additionally, we find that miR-146b-5p and miR-151a-5p significantly modulate tau seeding in tau biosensor cell model, highlighting their potential roles in tau pathology.