Authors
Roy, T., Ramesh, M., Nizam, N. A. A., Al-Chalabi, A., Iacoangeli, A., Al Kheifat, A.
Abstract
Human endogenous retrovirus K (HERV K) reactivation is increasingly implicated in amyotrophic lateral sclerosis (ALS), with ongoing clinical trials investigating antiretroviral therapies. However, there is a limited understanding of how HERV-K is trafficked in peripheral biofluids, and the role of exosomes, which are nano sized extracellular vesicles, in this process remains largely unexplored. Exosomes offer a stable and cell-specific cargo reservoir that may reflect central pathogenic processes and serve as a minimally invasive biomarker source. In this study, we isolated plasma-derived exosomes from ALS patients (n = 21) and healthy controls (n = 16), and quantified exosomal HERV-K gag, env, and pol transcript levels using SYBR Green qPCR with RNase treatment and normalization to both traditional and exosome enriched reference genes. HERV K pol expression was significantly elevated in ALS, with fold-changes ranging from 1.59 to 1.85 (P = 0.037 to 0.051). env and gag also showed increased expression, though with greater variability. Normalization to the exosome-specific gene SOD2 provided the most consistent signal. A trend toward higher pol expression in bulbar-onset ALS was observed. These findings suggest that exosomal HERV-K transcripts, particularly pol, could serve as accessible biomarkers for patient stratification and treatment monitoring in HERV K targeted ALS trials. This work establishes a proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration, supporting further investigation of liquid biopsy approaches in ALS precision medicine.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 11 Nov 2025.
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