Abstract

Differential Effects of APOE Genotype on Cerebrospinal Fluid Extracellular Vesicle miRNAs in Females vs. Males with Alzheimer's Disease

Julie Saugstad, Professor, Department of Anesthesiology & Perioperative Medicine, Oregon Health & Science University

Alzheimer’s disease (AD) is the most common form of dementia and the sixth-leading cause of death in the United States. We identified and validated miRNA biomarkers for Alzheimer's disease (AD) in cerebrospinal fluid (CSF) from living donors, then showed that five of the AD miRNAs trend down in expression from controls to mild cognitive impairment to AD. Our recent studies revealed that two biological risk factors for AD, sex and APOE e4 genotype, differentially effect CSF EV miRNA levels: APOE e4 within each sex altered distinct miRNAs, and predicted gene targets and pathways of the altered miRNAs are known to contribute to neurodegeneration in AD. We are currently establishing the physical features and molecular cargo of AD CSF EVs within the context of APOE genotype and sex, with the goal to identify novel gene targets of CSF EV miRNAs that are relevant to AD pathophysiology.