Alzheimer's disease (AD) in multiple sclerosis (MS): A systematic review of published cases, mechanistic links between AD and MS, and possible clinical evaluation of AD in MS

Background: Alzheimer's disease (AD) and multiple sclerosis (MS) are two neurological disorders that can pose enormous burden to a person's quality of life. Due to new therapeutic advancements that significantly extend the lifespan, there may be an increased prevalence of AD in elderly MS patients. Objective: Building on a previous review on MS-AD coexistence, this review not only aimed to broaden the pool of literature searched, but also investigated possible mechanistic links between clinical markers for MS and AD. Methods: We searched for newly reported cases of coexisting MS and AD in PubMed, Clinical Key, BioMed Central, and Europe PubMed Central databases; and identified 101 new cases in addition to the previously reported 24 cases by Luczynski et al. (2019). The resulting 125 comorbid cases necessitated an evaluation of literature on the pathogenesis of MS and AD. Results: This review highlights many overlaps between AD and MS (for instance, the immune cell dysfunction, glymphatic dysfunction, genetics, environmental factors, and others). We critically evaluated clinical and laboratory metrics used to identify AD in MS patients (e.g., MRI, amyloid-β and tau protein identification, miRNA biomarker evaluation, cerebrospinal fluid analysis, vitamin levels, gut microbiota etc.). Conclusions: Future research should refine these diagnostic criteria and focus on enhancing screening and detection methods for AD in MS patients. Furthermore, one should also investigate the primary causes of the increased comorbidity between AD and MS.