Plasma exosomal HERV-K transcripts are increased in amyotrophic lateral sclerosis

Area of Science:

• Neuroscience
• Virology
• Biochemistry

Background:

• Human endogenous retrovirus-K (HERV-K) reactivation is implicated in amyotrophic lateral sclerosis (ALS).
• The role of exosomes in trafficking HERV-K in peripheral biofluids is largely unexplored.
• Exosomes may serve as minimally invasive biomarkers reflecting pathogenic processes.

Purpose of the Study:

• To investigate the presence and levels of HERV-K transcripts within plasma-derived exosomes in ALS patients.
• To assess the potential of exosomal HERV-K transcripts as biomarkers for ALS.

Main Methods:

• Plasma exosomes were isolated from ALS patients (n=21) and healthy controls (n=16).
• Exosomal HERV-K gag, env, and pol transcript levels were quantified using SYBR Green qPCR.
• Normalization was performed using traditional and exosome-enriched reference genes, including SOD2.

Main Results:

• HERV-K pol transcript expression was significantly elevated in ALS patients compared to controls (fold-change 1.59-1.85, P=0.037-0.051).
• env and gag transcripts also showed increased expression with greater variability.
• Normalization to the exosome-specific gene SOD2 yielded the most consistent results.

Conclusions:

• Exosomal HERV-K transcripts, particularly pol, show potential as accessible biomarkers for ALS patient stratification and treatment monitoring.
• This study provides proof-of-concept for using exosomal cargo to track endogenous retroviral activity in neurodegeneration.
• Findings support further investigation of liquid biopsy approaches in ALS precision medicine.