Apolipoprotein E4 and its later-life health effects on the multiple sclerosis population
Multiple Sclerosis Journal – Experimental, Translational and Clinical, 2026
Zeldich D., Cheng C., Guan Y., Narain S., Koo B.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Background and objectives
Multiple sclerosis (MS) is a chronic autoimmune disease causing neuroinflammation and neurodegeneration. The apolipoprotein E4 (APOE4) allele, a major genetic risk factor for late-onset Alzheimer’s Disease, accelerates cognitive decline and neuroinflammatory processes, including blood–brain–barrier disruption. This study explores the impact of APOE4 on later-life health in MS patients using biomarkers from the UK Biobank.
Methods
MS patients were grouped by APOE4 carrier status: MS-E4 and MS-nonE4. Age- and sex-matched non-MS controls (control-E4, control-nonE4) were included for comparison. Analyses assessed retinal nerve fiber layer thickness (RNFL) from optical coherence tomography (OCT), blood biomarkers, cognitive performance, and brain magnetic resonance imaging (MRI) metrics.
Results
MS-E4 patients exhibited worse outcomes, including thinner RNFL, higher blood glial fibrillary acidic protein (GFAP) and neurofilament light chain levels, slower cognitive reaction times, and more white matter hyperintensities. GFAP had significant interactions between MS and APOE4 status, correlating with neurodegenerative markers.
Discussion
APOE4 exacerbates neurodegeneration and neuroinflammation in MS, evident in retinal OCT, cognitive testing, and MRI findings. Similar effects were observed in healthy APOE4 carriers. These results highlight the utility of multi-domain biomarkers for MS diagnosis and long-term management, emphasizing less invasive tools for monitoring disease progression.