Alcohol Intake Differentiates AD and LATE: A Telltale Lifestyle from Two Large-Scale Datasets

Alzheimer's disease (AD), as a progressive brain disease, affects cognition, memory, and behavior. Similarly, limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined common neurodegenerative disease that mimics the clinical symptoms of AD. At present, the risk factors implicated in LATE and those distinguishing LATE from AD are largely unknown. We leveraged an integrated feature selection-based algorithmic approach, to identify important factors differentiating subjects with LATE and/or AD from Control on significantly imbalanced data. We analyzed two datasets ROSMAP and NACC and discovered that alcohol consumption was a top lifestyle and environmental factor linked with LATE and AD and their associations were differential. In particular, we identified a specific subpopulation consisting of APOE e4 carriers. We found that, for this subpopulation, light-to-moderate alcohol intake was a protective factor against both AD and LATE, but its protective role against AD appeared stronger than LATE. The codes for our algorithms are available at https://github.com/xinxingwu-uk/PFV.