Project Grant RF1NS147442

The National Institute of Neurological Disorders and Stroke, part of the Department of Health and Human Services National Institutes of Health, awarded $1.878 million to Mayo Clinic Jacksonville on September 7, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853) to interrogate alpha-synuclein aggregate-associated proteomes and identify modifiers of Lewy body disease.

The project, running through August 31, 2029, employs proximity-dependent biotin identification and in situ probe-dependent proximity profiling to capture, identify, and differentiate intracellular proteins in proximity to soluble and insoluble alpha-synuclein under physiological and pathogenic conditions. In Aim 1, the recipient will use proximity-dependent biotin identification in live human neurons and mouse brain slices and employ quantitative mass spectrometry to isolate and identify biotinylated proteins associated with alpha-synuclein in human iPSC-derived neurons and glia and in murine organotypic brain slice cultures. In Aim 2, the recipient will use in situ probe-dependent proximity profiling in human postmortem brain tissue to probe the alpha-synuclein-associated proteome across different synucleinopathies including Lewy body dementia, Parkinson's disease, and multiple system atrophy. The work advances mechanistic understanding of alpha-synuclein's role in Alzheimer disease-related dementias by revealing key cofactors in aggregation and neurodegeneration processes. Place of performance is Jacksonville, Florida.