Electronic Thesis and Dissertation Repository


Master of Science


Anatomy and Cell Biology


Dr. Susanne Schmid


Amyotrophic lateral sclerosis with cognitive impairment (ALSci) can be characterized by pathological inclusions of microtubule associated protein tau (tau) uniquely phosphorylated at Thr175 (pThr175-tau). The purpose of this study was to characterize the behavioural consequences of expressing a pseudophosphorylated tau mimic of pThr175-tau (Thr175Asp-tau) in rat hippocampus. Expression was hypothesized to lead to pathological tau fibril formation resulting in cognitive and behavioural deficits. Expression was accomplished in female Sprague Dawley rats through stereotactic inoculations of recombinant adeno-associated virus (rAAV9) vector with human tau gene. Pathological tau fibrillary structures were identified, but behavioural testing up to 12 months post-surgery revealed no deficits in Thr175Asp-tau group when compared with the controls. Control inoculums included: wt-human tau, phosphorylation inhibition (Thr175Ala-tau), and green fluorescent protein. There were age-related behavioural changes across testing time points. This study serves an important step towards the development of an animal model for ALS with cognitive syndromes, which is essential for understanding disease progression.