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Peer-reviewedCC BY 4.0PLOS One

Abortive transcripts in exosomes - A potential biomarker for Alzheimer’s disease

  • Haizhu Wu1
  • Na Zhang2
  • Weiwei Yan3
  • Cailin Li4
  • Xiaomei Zhang
  • Xianglin Xv
  • Fang Fang
  • Shaowei Qin
  • Lifeng Zhao
4 affiliations
  1. 1Guilin Tourism University, School of Food and Health, Guilin, China
  2. 2Guilin Tourism University, Guangxi Engineering Research Center for Large-Scale Preparation & Nutrients and Hygiene of Guangxi Cuisine, Guilin, China
  3. 3Guilin Tourism University, Food Science and Technology Research Center, Guilin, China
  4. 4Guilin Medical University, School of Basic Medical Sciences, Guilin, China
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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.

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Cite

BibTeXRIS
BibTeX
@article{wu2026abortive,
  title = {{Abortive transcripts in exosomes - A potential biomarker for Alzheimer’s disease}},
  author = {Haizhu Wu and Na Zhang and Weiwei Yan and Cailin Li and Xiaomei Zhang and Xianglin Xv and Fang Fang and Shaowei Qin and Lifeng Zhao},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0357752},
  url = {https://doi.org/10.1371/journal.pone.0357752},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Abortive transcripts in exosomes - A potential biomarker for Alzheimer’s disease
AU  - Haizhu Wu
AU  - Na Zhang
AU  - Weiwei Yan
AU  - Cailin Li
AU  - Xiaomei Zhang
AU  - Xianglin Xv
AU  - Fang Fang
AU  - Shaowei Qin
AU  - Lifeng Zhao
PY  - 2026
DA  - 2026/09/11
JO  - PLOS One
DO  - 10.1371/journal.pone.0357752
UR  - https://doi.org/10.1371/journal.pone.0357752
AB  - 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.
SN  - 1932-6203
ER  -