2026 American Academy of Neurology Autoimmune Abstract Website

Federico Montini¹, Charles Spurlock², Christine Ryan³, Jessica Cooke Bailey⁶, Erika Trapl⁷, Guzel Shaginurova⁸, Lukasz Wylezinski⁹, Cheryl Sesler⁸, Mahboobeh Fereidan Esfahani¹⁰, Jessica Sagen¹¹, Hannah Gardener¹², Jacob McCauley¹², Alberto Caban-Martinez⁴, Roberta Brambilla⁵, Lilyana Amezcua¹³, William Oliver Tobin¹, Farren Briggs³
¹Mayo Clinic College of Medicine and Science, ²Decode Health, ³University of Miami Miller School of Medicine, ⁴Department of Public Health Sciences, ⁵Department of Neurological Surgery, University of Miami Miller School of Medicine, ⁶Department of Pharmacology and Toxicology, East Carolina University, ⁷Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, ⁸Decode Health, Inc., ⁹Decode Health Inc, ¹⁰Department of Neurology, The University of Texas at Austin Dell Medical School, ¹¹Mayo Clinic, ¹²University of Miami, ¹³USC

Objective:

To investigate per- and polyfluoroalkyl substance (PFAS) concentrations in MS, AQP4-NMOSD, and MOGAD.

Background:

PFAS are persistent immunotoxic/neurotoxic chemicals widely detectable in the US population and elevated in MS in Sweden.

Design/Methods:

Serum PFHxS, PFOA, and PFOS were quantified in ACP (73 untreated RRMS, 35 NMOSD, 106 HC) and CMSAN (103 RRMS, 22 SPMS, 28 PPMS, 24 NMOSD, 48 MOGAD). Linear regression tested MS vs HC in ACP, MS vs NMOSD in both cohorts, and MS vs MOGAD in CMSAN, adjusting for age, sex, BMI, and smoking for normalized PFAS (mean=0, SD=1), including sex-stratified models. In 56 ACP RRMS females, associations between PFAS and sex-steroid metabolites were evaluated, and PFAS-correlated gene-expression signatures were examined.

Results:

PFHxS was elevated in MS versus HC (ACP β=0.38, p=0.0025), NMOSD (ACP+CMSAN β=0.52, p=6.3×10⁻⁵), and showed a trend versus MOGAD (CMSAN β=0.31, p=0.058).

In females, PFHxS was higher versus HC (β=0.44, p=0.0058) and NMOSD (ACP+CMSAN β=0.53, p=0.00047), but not MOGAD (β=0.42, p=0.061); No significant differences were observed among males.

PFOA was not significantly elevated versus HC (ACP β=0.16, p=0.054), but was higher versus NMOSD (ACP+CMSAN β=0.76, p=6.8×10⁻⁹) and MOGAD (β=0.33, p=0.010).

Among females, PFOA showed a trend versus HC (β=0.24, p=0.075) and was higher versus NMOSD (ACP+CMSAN β=0.80, p=2.9×10⁻⁷) and MOGAD (β=0.60, p=0.013); males showed no differences.

PFOS did not differ versus HC (β=0.14, p=0.32) and was higher versus NMOSD (ACP+CMSAN β=0.64, p=3.3×10⁻⁷) but not MOGAD (β=0.08, p=0.60), with less consistent sex-specific patterns.

Exploratory analyses identified MS×PFOA interactions for several sex-steroid metabolites, and tentative enrichment of neuronal membrane pathways among PFAS-correlated genes.

Conclusions:

PFHxS and PFOA were elevated in MS versus HC, NMOSD, and MOGAD, specifically among females.

Exploratory findings suggest plausible pathways linking PFAS exposure to MS. Multi-ethnic and longitudinal studies are needed to expand generalizability and clarify temporality and causality.