Magdalena Ivanova, PhD

Investigator:

Magdalena Ivanova, PhD

Name of Institution:

University of Michigan, Ann Arbor, Michigan

Project Title:

Biochemical and structural studies of α-synuclein (αsyn) fibrils derived from brain tissues with Parkinson’s disease (PD) and Dementia with Lewy bodies (LB) with Alzheimer’s disease


Investigator Bio:

Dr. Ivanova is a Research Assistant Professor in the Department of Neurology and Adjunct Assistant Professor in the Program of Biophysics at University of Michigan, Ann Arbor. She received her PhD degree in the Institute of Molecular Biophysics at the Florida State University and completed a postdoctoral fellowship in the Molecular Biology Institute at the University of California, Los Angeles. Her current research focuses on defining the molecular determinants of protein aggregation and elucidating the toxicity that is associated with the aberrant aggregation of proteins.

Objective:

The goal of this proposal is to determine whether αsyn fibrils amplified by incubation with brain tissue of individuals with PD (αsyn in LB pathology only) and Dementia with Lewy bodies with Alzheimer’s disease (LB pathology and amyloid beta plaques) form different structures.

Background:

It is well known that some patients with neurodegeneration have ‘mixed’ brain pathologies in which the brain contains pathologic hallmarks of both PD (αsyn in LBs) and Alzheimer’s disease (amyloid beta plaques). Both of these proteins form aggregates, as one molecule induces its neighbor to fold into a shape that allows the molecules to clump together forming fibrils. Evidence suggests that αsyn and Amyloid beta can influence each-others’ aggregation patterns. This proposal seeks to determine whether aggregates derived from tissues of individuals with LBs only and those with both LBs and amyloid beta plaques exhibit different structures.

Methods/Design:

We will acquire frozen brains with LB only and LB with amyloid beta plaque pathology and purify the abnormal protein aggregates. We will then incubate αsyn manufactured in the lab with the brain tissues. We will then compare the characteristics of αsyn fibrils formed when incubated with each type of brain tissue.

Relevance to Diagnosis/Treatment of Parkinson’s disease:

The ultimate goal of this study is to understand the different types of αsyn fibrils formed and use them to design compounds that intervene with their formation. Any progress in this direction will enable a personalized approach to treatment of the LB associated brain disorders.