Relationships of Alzheimer’s disease and apolipoprotein E genotypes with small RNA and protein cargo of brain tissue extracellular vesicles

Abstract

Alzheimer’s disease (AD) is a public health crisis that grows as populations age. Hallmarks of this neurodegenerative disease include aggregation of beta-amyloid peptides and hyperphosphorylated tau proteins in the brain. Variants of the APOE gene are the greatest known risk factors for sporadic AD. As emerging players in AD pathophysiology, extracellular vesicles (EVs) contain proteins, lipids, and RNAs and are involved in disposal of cellular toxins and intercellular communication. AD-related changes in the molecular composition of EVs may contribute to pathophysiology and lend insights into disease mechanisms. We recently adapted a method for separation of brain-derived EVs (bdEVs) from post-mortem tissues. Using this method, we isolated bdEVs from AD patients with different APOE genotypes (n=23) and controls (n=7). bdEVs were counted, sized, and subjected to parallel small RNA sequencing and proteomic analysis. Numerous bdEV-associated RNAs and proteins correlated with AD pathology and APOE genotype. Some of the identified entities have been implicated previously in important AD-related pathways, including amyloid processing, neurodegeneration, and metabolic functions. These findings provide further evidence that bdEVs and their molecular cargo modulate development and progression of AD.

RNA landscapes of brain tissue and brain tissue-derived extracellular vesicles in simian immunodeficiency virus (SIV) infection and SIV-related central nervous system pathology

“…Recent advances by our group and others allow us to separate and characterize brain tissue-derived EVs (Huang et al, 2020a) (bdEVs) with a high degree of rigor. Exploring the molecular components of bdEVs may hint at mechanisms of CNS pathogenesis in the brain (Huang et al, 2022a(Huang et al, , 2020b.…”