Mouse models of cognitive deficits due to alpha-synuclein pathology.

Synucleopathies are neurodegenerative disorders characterized by abnormal accumulation of alpha-synuclein, most often in neurons. Familial forms are due to mutations or multiplications of the gene encoding for alpha-synuclein but most synucleopathies occur sporadically. They include Parkinson's disease (PD) and dementia with Lewy Bodies (DLB), which are both linked to cognitive decline. In DLB, dementia dominates the symptoms whereas in PD, subtle cognitive deficits are frequent and may appear even before motor symptoms, but only a fraction of patients develop severe dementia-type cognitive deficits. Several lines of mice were developed to model human synucleopathies by over-expressing the wild type or the mutated human alpha-synuclein under a variety of promoters. In addition, mice lacking alpha-synuclein have been used to determine the role of this protein in cognitive function. This chapter will review cognitive alterations observed in these models and discuss how they may help understand the various forms and stages of cognitive deficits observed in patients with synucleopathies.