2005 Investigator-Initiated Research Grant

Presenilin proteins play a fairly well-understood role in Alzheimer’s disease. They help clip the beta-amyloid protein fragment, a key suspect in Alzheimer pathology, from a larger molecule. Most cases of the rare inherited form of Alzheimer’s are, in fact, due to mutations in the genes for presenilins.

Recent studies suggests that presenilins may also be involved in the other key feature of Alzheimer’s disease, abnormal chemical changes in the tau protein and the subsequent formation of neurofibrillary tangles. A possible tau-affiliated function of presenilin suggests that presenilin may also play a role in neurodegenerative diseases that have tangles but no beta-amyloid deposits.

David E. Kang, Ph.D., and colleagues have hypothesized that changes in presenilin function may set in motion a chain of chemical events that contribute to abnormal changes in tau, tangle formation, and the degeneration of nerve cells. In studies with cultured cells, they will characterize the mechanism by which changes in presenilin function may contribute to tau pathologies. They will also examine genetically altered mice that carry mutated human presenilin genes to determine how these mutations influence the events leading to changes in tau properties. The findings may suggest new targets for developing disease-modifying treatments.