Twisting Away Toxic Proteins in Alzheimer's Disease

Tau aggregation is a major pathogenic factor in Alzheimer’s disease. Our studies have identified a family of proteins that alter tau aggregation, including one member of this family can disaggregate tau aggregates into smaller non-toxic entities. The goal of this proposal is to elucidate the mechanisms of this disaggregation towards the ultimate goal of designing therapeutic strategies that mimic this activity. These studies will identify the properties and number of members of this protein family that present this activity while simultaneously examining the properties of tau that facilitate toxic aggregation and accumulation.

Note: This grant was transferred by John Koren, PhD to Jose Abisambra, PhD as of July 1, 2021 when he left his institution for an industry position.

This project seeks to reverse the pathological accumulation of toxic proteins in Alzheimer’s Disease. There are three key portions: First, we will examine if certain proteins can work to accelerate, decelerate, or reverse how the tau protein accumulates in Alzheimer’s disease. We will take measurements on how these proteins affect the physical state of tau that drives Alzheimer’s disease progression. Second, we have data that at least one class of proteins we will examine can dramatically reverse the aggregation of tau commonly observed in Alzheimer’s disease.