Clinical features of older MS patients with and without Alzheimer disease biomarkers

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammatory demyelination and axonal injury. Magnetic resonance imaging (MRI) plays a central role in MS diagnosis. Recent work suggests that biomarkers indicative of Alzheimer's disease (AD) are markedly reduced in people with MS. Whether differences in AD biomarkers are related to different features of MS, including MRI characteristics or treatment history, is unclear. In this study, 100 MS patients from Washington University in St. Louis underwent review of their most recent MRI as well as their prior and present MS disease-modifying treatment (DMT) exposures. We then ascertained the relation of MRI features and DMT to plasma AD biomarker measurements, with only a small subset (N=7) demonstrating APS2+ biomarker evidence of AD. Lesion distribution across MS topographies and total white matter lesion (WML) burden were both similar across MS patients with and without biomarker evidence of AD. Central vein sign (CVS), a recently integrated imaging biomarker of MS, was highly prevalent across the MS cohort and did not differ by AD biomarker status or MS clinical typicality at diagnosis, supporting the MS diagnoses even for people with atypical initial presentations. DMT exposure history showed associations with AD biomarkers: longer exposure to B cell-depleting anti-CD20 monoclonal antibody therapies (BCDT) corresponded to lower levels of amyloid pathology as measured by plasma biomarkers, and longer exposure to interferon-beta corresponded to a less pathological Aβ42/40 ratio. These findings indicate that structural MRI features do not explain differences in AD biomarker profiles in MS, whereas treatment-related immunologic effects may contribute to variation in AD pathology risk in MS patients.