A multi‐omic approach to elucidate novel disease mechanisms and biomarkers for psychosis in Alzheimer’s disease

• Published in: Alzheimer's & dementia Vol. 19; no. S18
• Main Authors: Pishva, Ehsan, Kouhsar, Morteza P, Weymouth, Luke Stephen, Smith, Adam R., Wedatilake, Yehani, Torkamani, Ali, Sweet, Robert, Ballard, Clive G, Mill, Jonathan, Kofler, Julia, Bergh, Sverre, Selbæk, Geir, Lunnon, Katie, Creese, Byron
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• DOI: 10.1002/alz.070953
• ISSN: 1552-5260

Background Psychosis is a debilitating syndrome occurring in 40‐60% of people with Alzheimer’s disease (AD) and corresponds with a more severe disease course. Evidence suggests that psychosis in AD is associated with a distinct profile of microbiological changes, but little is known about the molecular processes driving etiology. Method Genome‐wide DNA methylation, small non‐coding (nc) RNAs (microRNA, transfer RNA, piwiRNA) and long coding and ncRNAs (mRNA, lincRNA, cicular RNAs) were quantified from 248 whole blood samples obtained from the Norwegian registry of persons assessed for cognitive symptoms (NorCog) cohort. Multi‐omics profiles of AD patients with psychosis (AD+P) were compared to the patients without psychosis (AD‐P). Result There were significant differences in DNA methylation, small ncRNAs, and long coding and ncRNAs between AD+P and AD‐P patients. Further analysis revealed specific genomic regions and molecular pathways that were differentially methylated or expressed in AD+P patients compared to AD‐P patients. Conclusion Our findings suggest that there may be distinct molecular signatures associated with AD psychosis, and that these differences may potentially be used as biomarkers for the early detection and diagnosis of AD psychosis.