Basic Science and Pathogenesis.

Background: In Alzheimer's disease (AD), changes in the brain transcriptome are hypothesized to mediate the impact of neuropathology on cognition. Gene expression profiling from postmortem brain tissue is a promising approach to identify causal pathways; however, there are challenges to definitively resolve the upstream pathologic triggers along with the downstream consequences for AD clinical manifestations.

Method: We have functionally dissected 30 AD-associated gene coexpression modules using a cross-species strategy in Drosophila melanogaster models.

Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism.