Fingerprinting In Vivo and In Vitro Prion Strains

Alzheimer’s Disease (AD) is associated with the misfolding of tau and Aβ proteins. AD shares important molecular characteristics with classical PrP prion diseases, including the induced misfolding of soluble proteins in an autocatalytic manner and the accumulation of insoluble amyloids. Different “conformational strains” of PrP give rise to different neurodegenerative diseases. Conformation sensitive dyes are used to rapidly screen and fingerprint these “conformational strains” of prion proteins.

My project goal is to fingerprint various prion strains in vivo as well as in vitro with molecules that light up when bound to prion fibrils. Prions are what make up the Aβ plaques and neurofibrillary tau tangles observed in the brains of Alzheimer’s and related neurodegenerative disease patients. Interestingly, how these prions assemble — prion conformation — gives rise to distinctive neurodegenerative disease. Herein, I develop technology to rapidly assess the degree of similarity of prion conformations. First aim describes the development of confocal imaging technology that rapidly assess prion conformations. Second aim fingerprints prion conformations from brain tissues and correlate its composition via proteome. Third aim develops a peptide that bind identified prion conformations. The outcome technology will provide rapid assessment of prion conformations at a macroscopic level, which are further correlated to brain region, disease type, and prion composition.