TY - JOUR T1 - α-Syn Suppression Reverses Synaptic and Memory Defects in a Mouse Model of Dementia with Lewy Bodies JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10076 LP - 10087 DO - 10.1523/JNEUROSCI.0618-11.2011 VL - 31 IS - 27 AU - Youngshin Lim AU - Victoria M. Kehm AU - Edward B. Lee AU - James H. Soper AU - Chi Li AU - John Q. Trojanowski AU - Virginia M.-Y. Lee Y1 - 2011/07/06 UR - http://www.jneurosci.org/content/31/27/10076.abstract N2 - Abnormally accumulated α-synuclein (α-syn) is a pathological hallmark of Lewy body-related disorders such as Parkinson's disease (PD) and dementia with Lewy body disease (DLB). However, it is not well understood whether and how abnormal accumulation of α-syn leads to cognitive impairment or dementia in PD and DLB. Furthermore, it is not known whether targeted removal of α-syn pathology can reverse cognitive decline. Here, we found that the distribution of α-syn pathology in an inducible α-syn transgenic mouse model recapitulates that in human DLB. Abnormal accumulation of α-syn in the limbic system, particularly in the hippocampus, correlated with memory impairment and led to structural synaptic deficits. Furthermore, when α-syn expression was suppressed, we observed partial clearing of pre-existing α-syn pathology and reversal of structural synaptic defects, resulting in an improvement in memory function. ER -