Potentiation of alpha-synnucleinopathy by amyloid beta in vivo

Michael Lee, PhD Johns Hopkins University

Project Details

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by neuronal abnormalities that are specific to each disease. In AD, a small portion of a larger protein called amyloid beta (Aß) is deposited outside the neurons to form insoluble “senile plaques.” There are also abnormal modifications of a protein called tau, which aggregates to form “tangles” inside the affected neurons. In PD, a protein called alpha-synuclein aggregates inside the neural cells to form Lewy bodies (LBs) and Lewy neurites (LNs). Recently, the careful analyses of these abnormalities suggested that LBs and LNs can be present in AD, and that the presence of “senile plaques” can cause more alpha-synuclein to form LBs in PD. The abnormalities in alpha-synuclein that are induced by “senile plaques” may cause greater damage to neurons, considering that abnormalities in alpha-synuclein are associated with neuronal damage in humans and mice. Dr. Lee is testing the hypothesis that “senile plaques” can induce LBs through biochemical alterations of alpha-synuclein. The results of this study will provide a foundation for understanding how “senile plaques” induce abnormalities in the alpha-synuclein, and how these abnormalities contribute to the neurodegeneration seen in AD and PD.