Catalyst Awardee

Project Description

Examining Evidence for Transmissible Alzheimer's Disease

Ajay Sriram Mathuru, Ph.D., and Jan Gruber, M.Sc., Ph.D., National University of Singapore

Competition Sponsor: Ministry of Health and National Research Foundation of Singapore

Alzheimer’s Disease (AD) is known to develop among many individuals in an age dependent manner. A few genetic variants in enzymes or proteins associated with production of amyloid beta (Aβ) peptide from Aβ protein have been identified as potential candidates associated with AD. However, for most part, it is unclear if some individuals are more susceptible than others. In the last 5 years, 2 studies have been published that suggest the possibility for Aβ plaque formation to be associated with seeding of contaminated Aβ plaques to healthy people. This is surprising and it is still debated if AD can be transmitted, just like a prion disease to provide nucleation sites that facilitates further misfolding and aggregation of Aβ peptides and tau proteins in the brain. Only a couple of studies have shown some evidence. Here we take the step to test if transmission can occur via ingestion of Aβ aggregates. We plan to test this transmissibility hypothesis by feeding genetically engineered laboratory model nematode that express the human Aβ aggregates to another laboratory model, the zebrafish. We will then examine the brains by histopathological techniques and the behavior of the fish to evaluate if Aβ associated toxicity and neurodegeneration is detectable due to transmission in a prion-like manner. We also plan to observe inter-generational transmission, if any, and the effectiveness of drug-combinations in attenuating any effects found.

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