Parkinson's disease and dementia with Lewy bodies are very frequent neurological 
disorders of the elderly. Mutations in the alpha-synuclein (alphaSYN) gene cause 
Parkinson's disease, often associated with dementia. Neuropathologically these 
diseases are characterized by the presence of Lewy bodies and Lewy neurites, 
intraneuronal inclusions mostly composed of alphaSYN protein fibrils. Moreover, 
alphaSYN is phosphorylated at S129 (phospho-serine-129 [PSer129]) in 
neuropathological lesions. Using our (Thy1)-[A30P]alphaSYN transgenic mouse 
model that develops age-dependent impairment in fear conditioning behavior, we 
investigated PSer129 immunostaining in the brain. We found distinct staining 
patterns using new, sensitive monoclonal antibodies. Somal and nuclear PSer129 
immunoreactivity increased with age in hippocampal and cortical areas as well as 
the lateral/basolateral amygdalar nuclei and was present also in young, 
pre-symptomatic mice, but not wild-type controls. The tendency of PSer129 
immunostaining to accumulate in the nucleus was confirmed in cell culture. 
(Thy1)-[A30P]alphaSYN transgenic mice further developed age-dependent, specific 
neuritic/terminal alphaSYN pathology in the medial parts of the central 
amygdalar nucleus and one of its projection areas, the lateral hypothalamus. 
Interestingly, this type of PSer129 neuropathology was thioflavine S negative, 
unlike the Lewy-like neuropathology present in the brain stem of 
(Thy1)-[A30P]alphaSYN mice. Thus, alphaSYN becomes phosphorylated in distinct 
parts of the brain in this alpha-synucleinopathy mouse model, showing 
age-dependent increases of nuclear PSer129 in cortical brain areas and the 
formation of neuritic/terminal PSer129 neuropathology with variable amyloid 
quality within the fear conditioning circuitry and the brain stem.