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Date of Award
Doctor of Philosophy (PhD)
Tauopathies have diverse presentation, progression, and neuropathology. They are linked to tau prion strains, self-replicating assemblies of unique quaternary conformation. Strains can be propagated indefinitely in cultured cells, and induce unique patterns of transmissible neuropathology upon inoculation in mice. Aggregates from a single strain reproduce only that strain upon re-inoculation into cells or mice. DS9 and DS10 cell lines propagate distinct synthetic strains. Surprisingly, DS9 monomer inoculated into naïve cells encoded an identical “sub-strain,” whereas DS10 monomer encoded multiple sub-strains. Sub-strains produced distinct pathology upon inoculation into a tauopathy mouse model (PS19). Brain-derived tau monomer from an Alzheimer’s brain encoded a single strain. Monomer from a corticobasal degeneration brain encoded three sub-strains in which monomer from each encoded all three upon re-inoculation into cells. Tau monomer thus adopts multiple, stable seed-competent conformations, each of which encodes a limited number of strains. This provides insights into the origins of distinct tauopathies.
Chair and Committee
Marc I. Diamond
Conrad Weihl, Meredith Jackrel, Timothy Miller, Rohit Pappu,
Sharma, Apurwa, "Tau monomer encodes Strains" (2018). Arts & Sciences Electronic Theses and Dissertations. 1684.
Available for download on Thursday, December 15, 2118