Studying Human Alpha-synuclein in Mice

We have been using human A53T mutant alpha-synuclein transgenic mice in our effects to generate a mouse model of Parkinson's disease that recapitulates the progressive nature of the disease and in which all the regions of the nervous system that are affected in humans are also affected in mouse. Our disease modeling is now incorporating the recently discovered prion-like nature of misfolded alpha-synuclein, with the goal of developing earlier disease onset in the mice. A good progressive animal model of Parkinson's disease will be useful for identification of early disease biomarkers and for testing methods to slow or prevent disease progression.Neurons from transgenic mice expressing human mutant alpha-synuclein. alpha-synuclein inclusions are in red, and Fluoro-Jade B positive neurons (bright green cytoplasm) are undergoing neurodegeneration. DAPI (blue) marks cell nuclei.Many neurodegenerative diseases have features in common, such as mitochondrial disfunction and glial activation. Though not commonly appreciated, Parkinson's disease can progress to dementia, and there are some links between alpha-synuclein and Alzheimer's disease. Using mice transgenic for both a mutant form of APP that causes a rare familial form of Alzheimer's disease and the human A53T mutant alpha-synuclein, we are investigating what role if any alpha-synuclein in Alzheimer plaque formation.