Unlocking the Secrets of Alzheimer’s Disease with Psychosis

Unlocking the Secrets of Alzheimer’s Disease with Psychosis: The Multi-Omic Approach to Psychosis in Alzheimer’s Disease (MOA-PAD) Study

Published in the February 2025 Alzheimer’s & Dementia, A brain DNA co-methylation network analysis of psychosis in Alzheimer’s disease investigates the distinct molecular and neuropathological profiles associated with psychosis in Alzheimer’s disease by analyzing brain DNA co-methylation networks. The corresponding MOA-PAD Study contributes epigenetic data to the research community to advance the study of Alzheimer’s disease with psychosis.

The contribution represents DNA methylomic data generated in the Pittsburgh Alzheimer’s Disease Research Center (PITT-ADRC) cohort and includes 113 individuals that had Alzheimer’s disease with psychosis, and 40 that had Alzheimer’s disease without psychosis. 

Part of the NIA funded Psych-AD Program, the data help illuminate how the epigenetic profile of individuals with Alzheimer’s disease and psychosis differ from that of people with Alzheimer’s disease without psychosis.

“We’re interested in psychosis and Alzheimer’s because of its distinct prognosis,” said Katie Lunnon, a Professor in Dementia Genomics at the University of Exeter and the study’s Principal Investigator.

Dr. Katie Lunnon

“Patients with psychosis tend to experience a more rapid disease progression,” she said, “it is relatively common, with around 50% of people with the disease experiencing psychosis.” 

MOA-PAD seeks to identify the underlying mechanisms that are involved in the development of psychosis in Alzheimer’s disease. The study also aims to discover new biomarkers, specifically in blood samples, that could predict the progression of the disease and the development of psychosis. 

Professor Lunnon and her team will be sharing matched genetic variation data, RNA sequencing, and microRNA sequencing data in the same samples, allowing for comprehensive comparisons across various genomic layers in the same individuals. By undertaking this multi-omics approach, they hope to uncover new disease mechanisms that could lead to the development of innovative drugs and predictive biomarkers. 

The potential impact of these layers of genomic information on Alzheimer’s disease research is substantial. Professor Lunnon hopes the discoveries will lead to validation, meta-analysis, and an awareness of the unique challenges posed by psychosis in Alzheimer’s disease.

“We all share this goal of trying to understand Alzheimer’s disease,” said Professor Lunnon, “and I love that we’re able to collaborate to identify novel disease mechanisms that might be really important in the long run for people with dementia.”