Center On Alpha-synuclein Strains In Alzheimer Disease & Related Dementias

The Lewy body diseases (PD, DLB, and MSA) likely begin with the abnormal accumulation of soluble ɲ-synuclein monomers as insoluble fibrils. This process also likely occurs in AD and other neurodegenerative diseases where Lewy bodies and Lewy neurites can be found. The clinical prognosis of these patients might depend on the levels of ɲ-synuclein fibrils, but early detection of fibrilized forms of ɲ-synuclein in plasma and / or CSF is challenging since the levels of these proteins are low and distinguishing fibrils from monomers is difficult. Recently, we have developed an ELISA assay that can distinguish healthy ɲ-synuclein monomers from ɲ-synuclein fibrils. These assays were developed by the PI of this project at the U Penn as part of a U19 program focusing on ɲ-synuclein strains in Alzheimer’s Disease and Related Dementias (U19 AG062418), wherein the PI is a co-Investigator. At Northwestern, the PI will further develop and validate these assays using monoclonal antibody reagents and patient samples generated at U Penn. We will also attempt to replicate our preliminary results using patient samples generated at Northwestern. These studies are critical stepping stones towards translating ɲ-synuclein fibril based biomarkers to clinical practice.