biostudies-literatureCleary JANIA NIH HHSNancy and Buster Alvord Endowmente70597https://www.ebi.ac.uk/biostudies/studies/S-EPMC12441806biostudies-literatureUnknown21(9)<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Analysis of miRNAs in brain tissue and their sEV revealed significant and concordant dysregAlzheimer's & dementia : the journal of the Alzheimer's AssociationMicroRNA cargo in neuron-derived vesicles as peripheral biomarkers of brain insulin dysregulation.PMC12441806R01 AG061805U24AG072458U19AG0665673R01AG058571-02S11R21 AG075611P30AG0665091RF1AG068629Craft SCleary JAEspeland MADing JHarrison WHsu FCHoward MDeep GSu YSingh SKeene CDHayden KMKumar AfalseMicroRNA cargo in neuron-derived vesicles as peripheral biomarkers of brain insulin dysregulation.<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Analysis of miRNAs in brain tissue and their sEV revealed significant and concordant dysreg2025-01-01T00:00:00Z2025 Sep2026-06-03T11:25:02.155Z2026-04-27T03:10:27.098ZS-EPMC124418064096006110.1002/alz.70597