Kayla Pate

Alzheimer’s disease (AD) is the most common form of dementia and is caused by the aggregation of the amyloid-β (Aβ) protein, resulting in the formation of extracellular senile plaques in the brain. While Aβ monomer occurs naturally in blood, plasma, and cerebrospinal fluid (CSF), Aβ aggregates, particularly oligomers, induce cellular toxicity. Several CSF proteins may naturally sequester Aβ aggregation, with one of the most promising being transthyretin (TTR). TTR has been shown to bind to Aβ, inhibit Aβ aggregation, and reduce Aβ toxicity. This has led our lab to synthesize a series of cyclic conformationally constrained peptide mimics of TTR that can bind to Aβ thereby inhibiting aggregation.

I am currently evaluating the therapeutic potential of our most promising cyclic peptide, cG8. Ongoing studies include determining its stability and binding to Aβ under physiologically relevant conditions. I am also evaluating the ability of cG8 to inhibit the aggregation of other amyloidogenic proteins involved in diseases such a type II diabetes and Parkinson’s disease. Future studies will use human neurons derived from iPSCs to determine if and by what mechanism cG8 reduces Aβ-induced cellular toxicity.