title: T-Tau and P-Tau in Brain and Blood from Natural and Experimental Prion Diseases.
abstract: Synaptic abnormalities are prominent in prion disease pathogenesis and are responsible for functional deficits. The microtubule associated protein, Tau, binds to and stabilizes microtubules in axons ensuring axonal transport of synaptic components. Tau phosphorylation reduces its affinity for microtubules leading to their instability and resulting in disrupted axonal transport and synaptic dysfunction. We report on the levels of total Tau (T-Tau) and phosphorylated Tau (P-Tau), measured by highly sensitive laser-based immunoassays, in the central nervous system and biofluids from experimentally transmitted prion disease in mice and natural cases of sporadic Creutzfeldt-Jakob Disease (sCJD) in humans. We found that, in contrast to sCJD where only the levels of T-Tau in brain are increased, both T-Tau and P-Tau are increased in the brains of symptomatic mice experimentally infected with the ME7, 139A and 22L mouse-adapted scrapie strains. The increased levels of T-Tau in sCJD brain, compared to control samples, were also observed in patient plasma. In contrast, there was no detectable increase in T-Tau and P-Tau in plasma from symptomatic experimentally infected mice. Furthermore, our data suggests that in mice showing clinical signs of prion disease the levels and/or ratios of T-Tau and P-Tau are only a useful parameter for differentiating the mouse-adapted scrapie strains that differ in the extent of disease. We conclude that the neuropathogenesis associated with P-Tau and synaptic dysfunction is similar for at least two of the mouse-adapted scrapie strains tested but may differ between sporadic and experimentally transmitted prion diseases.
authors.affiliation: Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Rubenstein
authors.affiliation: Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
authors.forename: Binggong
authors.initials: B
authors.lastname: Chang
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Petersen
authors.affiliation: Department of Neurology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
authors.forename: Allen
authors.initials: A
authors.lastname: Chiu
authors.affiliation: Litwin-Zucker Center for Research in Alzheimer's Disease, Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D023902:Chromosome Pairing / Q000502:physiology; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000502:physiology; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D011328:Prions; D016875:tau Proteins