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(Supplement) Exploring the Mechanisms by which Co-pathologies Drive Neuroinflammation and Progression in Parkinson’s Disease

This grant builds upon the research from a prior grant: Co-Pathologies Drive Neuroinflammation and Progression in PD

Study Rationale: Although Parkinson’s disease (PD) is considered a synucleinopathy, the clinical progression of PD is driven by additional pathological proteins such as tau and beta amyloid. We hypothesize that these pathologies, in concert, drive brain inflammation that may differ in character or quantity than that triggered by alpha-synuclein alone. In this project, we will generate novel, nonhuman primate models of co-pathology and inflammation. We will then validate these models by comparing our findings to inflammatory processes seen in human brain samples, and we will validate the mechanisms involved by blocking these pathologies in animals using specific immunotherapies.

Hypothesis: We hypothesize that inducing co-pathologies will provide a more valid and constructive preclinical models for the human disease, and thus offer a superior model for the evaluation of future novel therapies.

Study Design: We will treat nonhuman primates with preformed alpha-synuclein fibrils, tau and beta-amyloid protein, and we will study the effects of these co-pathologies on specific inflammatory processes. In addition, we will study the effects of blocking these pathologies in mice and monkey models of co-pathologies with antibodies against alpha-synuclein, tau and beta-amyloid.

Impact on Diagnosis/Treatment of Parkinson’s disease: The failure to have discovered disease modified treatments for PD may in large part be due to the failure to create relevant animal models to test novel therapeutic strategies. The preclinical models we validate in this project along will provide essential platforms for testing novel therapeutic strategies.

Next Steps for Development:We will use our preclinical co-pathology models to test experimental therapies that are based upon inflammatory and non-inflammatory mechanisms, paving the way to combinatorial therapeutics.


  • Jeffrey H. Kordower, PhD

    Chicago, IL United States

  • Warren D. Hirst, PhD

    Cambridge, MA United States

  • Ashley S. Harms, PhD

    Birmingham, AL United States

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