Authors
Haizhu Wu, Na Zhang, Weiwei Yan, Cailin Li, Xiaomei Zhang, Xianglin Xv, Fang Fang, Shaowei Qin, Lifeng Zhao
Published in
PloS one. Volume 21. Issue 9. Pages e0357752. Epub Sep 11, 2026.
Abstract
Diagnosis of Alzheimer's disease (AD) relies on invasive cerebrospinal fluid analysis or costly neuroimaging, underscoring the need for minimally invasive blood-based biomarkers for early detection. Exosomes, promising biomarker carriers, are unexplored for ultra-short RNA species like abortive transcripts (ATs). We investigated whether 8-nucleotide ATs are selectively packaged into exosomes to reflect brain transcriptional dysregulation in AD. Using a transgenic AD mouse model and Aβ-stimulated BV2 microglia coupled with Base-Stacking Hybridization Assisted Ligation (BSHAL), we detected significant dysregulation of ATs from AD-relevant genes (Nefl, Bace1, Tyrobp, Ccl2, Pf4) in brain tissue; specifically, Bace1, Tyrobp, and Pf4 ATs showed robust increases (2.21-fold to 17.50-fold). These dysregulated AT signatures were mirrored in peripheral blood exosomes: Bace1, Tyrobp, and Pf4 ATs increased 10.58-, 38.72-, and 11.63-fold, respectively. Aβ-activated microglia demonstrated exosome-specific enrichment of ATs, particularly Pf4 ATs (~3510-fold increase), confirming active exosomal packaging. Exosomal ATs confer cell-type specificity for central nervous system pathology, lipid bilayer-enhanced stability, and sensitivity to transcriptional changes preceding pathological aggregation. Our findings, obtained in a transgenic mouse model and an in vitro microglial system, establish exosomal ATs as a novel class of blood-based biomarkers with potential for early AD diagnosis, pending validation in human cohorts.
PMID:
42726720
Bibliographic data and abstract were imported from PubMed on 12 Sep 2026.
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