A Transgenic Mouse Model of Dementia With Lewy Bodies Suggests A Link Between α-Synuclein Expression, Presynaptic Vesicle Pathology and Cognitive Deficit

Evaluation of: Lim Y, Kehm VM, Lee EB et al. α-syn suppression reverses synaptic and memory defects in a mouse model of dementia with Lewy bodies. J. Neurosci. 31, 10076–10087 (2011). This study reports on the regional and time-dependent pathological changes of mice expressing human wild-type or A53T-mutant α-synuclein under the control of a CaMKIIα promoter as well as a tetracycline-regulated transactivator. The transgene was turned on from postnatal day 21 onwards. A53T-mutant α-synuclein expression leads to a dementia with Lewy body-like phenotype. A presynaptic α-synuclein-related pathology goes hand-in-hand with memory impairment as measured by conditioned fear. By turning off the α-synuclein transgene at a particular time point after a synaptic pathology has already been developed, a regression of the α-synuclein-related changes can be observed and the memory impairment does not progress or even mildly improves.