Exploratory associations between APOE-ε4 carrier status and facial neuromuscular activity in cognitively intact adults: a cross-sectional surface electromyography study.

Authors

Marziye Eshghi, Panying Rong, Mehrdad Dadgostar, Hyunmin Shin, Brian D Richburg, Nelson V Barnett, David H Salat, Steven E Arnold, Jordan R Green

Published in

Frontiers in neurology. Volume 17. Pages 1740391. Epub Sep 23, 2026.

Abstract

The APOE-ε4 allele is a genetic risk factor for late-onset Alzheimer's disease (AD). Beyond cognitive decline, APOE-ε4 affects motor function, reducing muscle strength and coordination, potentially through mitochondrial dysfunction and oxidative stress. This study examined the influence of the APOE-ε4 allele on neuromuscular function in oral muscles involved in speech production, using surface electromyography (EMG); and evaluated the preliminary discriminatory performance of EMG-based multivariable models in differentiating APOE-ε4 carriers from noncarriers.
Forty-two cognitively intact adults (16 APOE-ε4 carriers, 26 noncarriers) completed speech tasks while EMG was recorded from seven craniofacial muscles. Seventy EMG features including amplitude, frequency, complexity, regularity, and functional connectivity were extracted. Statistical analyses assessed genotype effects, sex differences, and correlations with blood metabolic biomarkers, alongside group comparisons on cognitive measures to confirm preserved cognition in this sample.
APOE-ε4 carriers exhibited descriptive patterns consistent with increased motor unit recruitment and synchronization, indicating altered neuromuscular control and possible compensatory adjustments. Multivariable EMG-based models showed promising internal discrimination between carriers and noncarriers, whereas standard cognitive measures did not demonstrate significant APOE-ε4-related differences in this cohort. EMG-based measures also showed correlation with metabolic biomarkers. Genotype and genotype-by-sex effects on the EMG-derived factors were not statistically significant. However, descriptive sex-stratified patterns suggested reduced functional connectivity in female carriers and increased functional connectivity in male carriers.
These findings suggest that speech-based neuromuscular changes may serve as exploratory candidate indicators of neuromuscular vulnerability associated with APOE-ε4 carrier status in cognitively intact adults. While this study distinguishes APOE-ε4 carriers from noncarriers, further work is needed to determine whether these EMG features can diagnose AD, predict progression to mild cognitive impairment (MCI) or dementia, or serve as early diagnostic or prognostic biomarkers. Additionally, their prognostic value and relationship to standard cognitive measures should be confirmed in equivalent models and in larger, independent longitudinal cohorts.

PMID:
42845916
Bibliographic data and abstract were imported from PubMed on 08 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.