Immunotherapy Targeting Parkinson's Disease Transmission in Animal Models
|John Q. Trojanowski, MD, PhD
The project will determine if unique synthetic a-syn PFF strains characterized by Project III differentially transmit LBD and cross-seed tau NFTs following injection into the brains of M83 mice, using methods established in our laboratory to assess behavior, neuropathology and cerebrospinal fluid (CSF) levels of a-syn and tau in these mice.
We will also determine if enriched fractions of LBs/LNs from PD substantia nigra (SN) versus PDD/DLB cingulate cortex (CC) contain distinct a-syn strains that differentially transmit LBD and cross-seed tau NFTs following injection into the brains of M83 mice using the same methods as in Aim 1.
Finally, we will conduct proof of concept (POC) studies in M83 mice injected with pathological a-syn to determine if immunization with monoclonal antibodies (MAbs), identified by Project III to neutralize a-syn transmission, abrogates induction and spread of a-syn pathology in vivo.
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