{"id":"doi:10.1002/alz.71903","kind":"article","title":"miR-214-3p and NCKAP1: A microglial functional dimension of Alzheimer's progression","authors":["Noh MY","Moon Y","Kang S","Moon WJ","Kim HJ","Seo SW","Ahn S","Kang MH","Kim YS","Kim H","Bae JS","Jin HK","Choi H","Koh SH","Park KH","Day GS","Bu G","Kim SH"],"author_count":18,"year":2026,"published":"2026-10-01","venue":"Alzheimer's & dementia : the journal of the Alzheimer's Association","cited_by":0,"doi":"10.1002/alz.71903","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/alz.71903","archive_url":"https://space-kitty.com/papers/doi:10.1002/alz.71903","updated":null,"pmid":"42841306","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Introduction Biological Alzheimer's disease (AD) pathology does not fully explain the marked heterogeneity in clinical severity or progression. We investigated whether patient-derived induced microglia-like cell (iMG) profiles capture a functional dimension of AD progression beyond conventional plasma biomarkers. Methods We studied 114 participants comprising amyloid-negative healthy controls (n = 18) and amyloid-positive AD-continuum groups (cognitively unimpaired, n = 2; mild cognitive impairment, n = 18; AD dementia, n = 76). Plasma biomarkers, patient-derived iMG phagocytic function, and molecular markers were measured from the same blood draw. Longitudinal clinical follow-up was available in 102 participants, and paired baseline/follow-up blood samples were analyzed in a longitudinal biomarker cohort (n = 38). Results iMG phagocytic capacity progressively declined across the AD continuum, accompanied by reduced NCK-associated protein 1 (NCKAP1) expression and the strongest association with plasma glial fibrillary acidic protein (GFAP). Baseline NCKAP1 primarily reflected current cognitive impairment, whereas plasma miR-214-3p independently predicted faster cognitive decline beyond plasma tau phosphorylated at threonine 217 (p-tau217), GFAP, neurofilament light chain (NfL), age, and baseline cognition. Within amyloid-positive AD dementia, plasma miR-214-3p identified rapidly progressive disease and substantially improved prognostic discrimination beyond conventional plasma biomarkers. Longitudinally, declining NCKAP1 and increasing plasma miR-214-3p tracked the rate of cognitive deterioration, whereas plasma p-tau217, GFAP, and NfL changed over time but did not track disease tempo. Discussion Patient-derived iMG profiling identifies microglial phagocytic dysfunction as a complementary functional dimension of AD progression beyond conventional plasma biomarkers. Longitudinal microglial dynamics tracked disease tempo more closely than conventional plasma pathology markers and may help interpret biological-clinical discordance, supporting biologically informed staging, prognosis, and patient stratification in AD.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"miR-214-3p and NCKAP1: A microglial functional dimension of Alzheimer's progression\" by Noh MY, Moon Y, Kang S et al., https://doi.org/10.1002/alz.71903, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}