Abstract :Morris M, Koyama A, Masliah E, Mucke L (2011)
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 a -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 a-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.