Posterior cingulate cortex microRNA dysregulation differentiates cognitive resilience, mild cognitive impairment, and Alzheimer's disease DOI Creative Commons
Scott Counts, John S. Beck, Bryan Maloney

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role miRNAs during progression AD, including resilience and prodromal syndromes such mild cognitive impairment (MCI), remains underexplored. METHODS We performed miRNA‐sequencing on samples posterior cingulate cortex (PCC) obtained post mortem from Rush Religious Orders Study participants diagnosed ante with no (NCI), MCI, or AD. NCI subjects were subdivided low pathology (Braak stage I/II) high III/IV), suggestive resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, AD risk modeling. RESULTS identified specific miRNA groups, mRNA targets, signaling distinguishing resilience, neuropsychological test performance, neuropathological burden, risk. DISCUSSION These findings highlight potential harnessing to manipulate disease‐modifying implications for precision medicine. Highlights (MiRNA) dysregulation well‐established feature Novel also distinguish putative MiRNAs correlate performance burden. Select are associated age significant covariate. MiRNA include insulin, prolactin, kinases, neurite plasticity.

Language: Английский

Posterior cingulate cortex microRNA dysregulation differentiates cognitive resilience, mild cognitive impairment, and Alzheimer's disease DOI Creative Commons
Scott Counts, John S. Beck, Bryan Maloney

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(2)

Published: Feb. 1, 2025

Abstract INTRODUCTION MicroRNA (miRNA) activity is increasingly appreciated as a key regulator of pathophysiologic pathways in Alzheimer's disease (AD). However, the role miRNAs during progression AD, including resilience and prodromal syndromes such mild cognitive impairment (MCI), remains underexplored. METHODS We performed miRNA‐sequencing on samples posterior cingulate cortex (PCC) obtained post mortem from Rush Religious Orders Study participants diagnosed ante with no (NCI), MCI, or AD. NCI subjects were subdivided low pathology (Braak stage I/II) high III/IV), suggestive resilience. Bioinformatics approaches included differential expression, messenger RNA (mRNA) target prediction, interactome modeling, functional enrichment, AD risk modeling. RESULTS identified specific miRNA groups, mRNA targets, signaling distinguishing resilience, neuropsychological test performance, neuropathological burden, risk. DISCUSSION These findings highlight potential harnessing to manipulate disease‐modifying implications for precision medicine. Highlights (MiRNA) dysregulation well‐established feature Novel also distinguish putative MiRNAs correlate performance burden. Select are associated age significant covariate. MiRNA include insulin, prolactin, kinases, neurite plasticity.

Language: Английский

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