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In contrast to Parkinson's disease, the underlying pathology displays aggregation of the protein tau, which is also seen in disorders such as Alzheimer's disease. Currently, there are no pharmacological treatments for PSP, and drug discovery efforts are hindered by the lack of an animal model specific to PSP. Based on previous results and clinical pathology, it was hypothesized that viral deposition of tau in cholinergic neurons within the hindbrain would produce a tauopathy along neural connections to produce PSP\u2010like symptomology and pathology. By using a combination of ChAT\u2010CRE rats and CRE\u2010dependent AAV vectors, wildtype human tau (the PSP\u2010relevant 1N4R isoform; hTau) was expressed in hindbrain cholinergic neurons. Compared to control subjects (GFP), rats with tau expression displayed deficits in a variety of behavioural paradigms: acoustic startle reflex, marble burying, horizontal ladder and hindlimb motor reflex. Postmortem, the hTau rats had significantly reduced number of cholinergic pedunculopontine tegmentum and dopaminergic substantia nigra neurons, as well as abnormal tau deposits. This preclinical model has multiple points of convergence with the clinical features of PSP, some of which distinguish between PSP and Parkinson's disease.<\/jats:p>","DOI":"10.1111\/ejn.15496","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T17:59:13Z","timestamp":1634752753000},"page":"7688-7709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Human wildtype tau expression in cholinergic pedunculopontine tegmental neurons is sufficient to produce PSP\u2010like behavioural deficits and neuropathology"],"prefix":"10.1111","volume":"54","author":[{"given":"Gabriella","family":"King","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University at Buffalo  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaliana M.","family":"Veros","sequence":"additional","affiliation":[{"name":"Department of Pharmacology 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