Age-dependent cognitive decline and amygdala pathology in α-synuclein transgenic mice

Intraneuronal α-synuclein (αSYN) inclusions constitute the hallmark lesions of a number of neurodegenerative diseases, including Parkinsonʹs disease and dementia with Lewy bodies. In a transgenic mouse model expressing mutant [A30P]αSYN under control of the pan-neuronal Thy1 promoter, motor impairment became significant beyond 17 months of age. Cognitive performance was measured in the Morris water maze and upon fear conditioning. At 4 months of age, transgenic mice performed like controls. However, performance in these tasks was significantly impaired in (Thy1)-h[A30P]αSYN mice at 12 months of age. After completion of the cognition tests, mice were sacrificed and the regional distribution of neuropathology was examined. In contrast to 4 months old animals, 12 months old transgenic mice showed α-synucleinopathy in several brain regions, including the central nucleus of the amygdala, which is involved in cognitive behavior of mice, and is susceptible to αSYN pathology in human patients. Thus, age-dependent fibrillization of αSYN in specific cortical regions concomitant with cognitive decline may reflect dementia with Lewy bodies in a transgenic mouse model.