Jacob Alexander Cleary, Ashish Kumar, Yixin Su, Sangeeta Singh, Fang-Chi Hsu, Suzanne Craft, William Harrison, C. Dirk Keene, Marjorie Howard, Kathleen M. Hayden, Mark A. Espeland, Jingzhong Ding, Gagan Deep
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Subsequently, miRNA expression was analyzed in plasma neuron-derived sEV (NDE) of a second cohort consisting of cognitively normal and adjudicated mixed dementia (aMD) subjects, all with type 2 diabetes.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Analysis of miRNAs in brain tissue and their sEV revealed significant and concordant dysregulation. 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MicroRNA cargo in neuron-derived vesicles as peripheral biomarkers of brain insulin dysregulation
INTRODUCTION
Brain insulin resistance (bIR) is a risk factor for Alzheimer's disease (AD). However, the association between bIR and peripheral insulin resistance and their effects on cognition remains unclear.
METHODS
Here, we analyzed the expression of key genes (n = 84) involved in insulin signaling in brain tissue collected from healthy and AD subjects, as well as regulatory microRNAs (miRNAs) in the brain tissue and tissue-derived small extracellular vesicles (sEV). Subsequently, miRNA expression was analyzed in plasma neuron-derived sEV (NDE) of a second cohort consisting of cognitively normal and adjudicated mixed dementia (aMD) subjects, all with type 2 diabetes.
RESULTS
Analysis of miRNAs in brain tissue and their sEV revealed significant and concordant dysregulation. NDE demonstrated similar changes in specific miRNA expression, with significant upregulation exclusively in male aMD subjects, and showed correlation with cognition and plasma β-amyloid (Aβ) 1-40 and Aβ1-42.
DISCUSSION
NDE may serve as a liquid biopsy to determine sex-specific bIR and cognitive impairment.
Highlights
Insulin signaling is disrupted in brain tissue with Alzheimer's disease (AD).
microRNAs (miRNAs) regulate insulin signaling and insulin resistance.
miRNAs in neuron-derived small extracellular vesicles (sEV) could serve as biomarkers for brain insulin signaling.
Brain insulin signaling biomarkers in neuron-derived sEV (NDE) could predict cognitive impairment.
Sex-specific differences exist in brain insulin resistance biomarkers.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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