Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease.
Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or transgene-mediated neuronal expression of human wildtype α-synuclein. Both models were evaluated on Tau(+/+), Tau(+/-) and Tau(-/-) backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum. Similarly, tau reduction did not prevent motor deficits in α-synuclein transgenic mice. Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition.
Gladstone Institute of Neurological Disease, San Francisco, California, United States of America.
Meaghan
M
Morris
Akihiko
A
Koyama
Eliezer
E
Masliah
Lennart
L
Mucke
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000172:deficiency / Q000378:metabolism*
D051844:alpha-Synuclein; D016875:tau Proteins