Objective To explore changes in motor coordination, cognitive function, and anxiety-like behavior as well as pathological characteristics in α-synuclein A53T transgenic mice. Methods We used α-synuclein A53T transgenic mice with a C57BL/ 6 background as the experimental group, and included a negative control group. The open field and cylinder tests were used to examine mouse anxiety levels, the rotarod and grip tests were used to evaluate movement disorders, and the Morris water maze and a fear conditioning test were used to evaluate cognitive ability. Pathological features were studied using immunohistochemical staining and mitochondrial morphology was observed via electron microscopy. Results Compared with the control group, α-synuclein A53T transgenic mice moved a greater distance, indicating that the mice were overactive. Further, freezing time was decreased, indicating cognitive impairment. We found no differences in performance in the cylinder test, rotarod test, grip test, or Morris water maze. In the α-synuclein A53T transgenic mice, levels of phosphorylated α-synuclein in the substantia nigra, striatum, piriform cortex, and hippocampus were increased, and we found Lewy bodies in the prefrontal cortex. Further, increased deposition of α-synuclein in the substantia nigra and striatum was observed, and the number of TH cells in the substantia nigra decreased significantly. Compared with the control group, mitochondria fission in the amygdala was increased, and the mitochondrial contents were unclear. Conclusions Cognitive function was impaired in α-synuclein A53T transgenic mice. Pathological characteristics included α-synuclein / LBs deposits in the prefrontal and piriform cortex, decreases in dopaminergic neurons in the substantia nigra, and altered mitochondrial morphology in the amygdala. α-synuclein A53T transgenic mice may be an appropriate model of synucleinopathy-related cognitive disease such as Lewy body dementia and dementia related to Parkinson’s disease.