Project Grant RF1NS145135

Duke University's Office of Research Administration received a $1.8M Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), awarded on May 11, 2026, with completion targeted for April 30, 2029. The research project investigates LRRK2 (Leucine-Rich Repeat Kinase 2) signaling pathways and their role in Parkinson's disease (PD) and dementia progression. The research team will employ ultra-sensitive single molecule array assays to assess LRRK2 signaling biomarkers in biobanked tissues and biological fluids, with the primary objective of determining whether LRRK2 signaling changes predict disease severity, identifying associated molecular pathways, and characterizing how LRRK2 signaling alterations manifest with progressive pathological deposits of alpha-synuclein and tau proteins in the brain.

The project directly addresses a significant gap in human-based understanding of LRRK2 signaling in neurological disease progression. Preliminary findings suggest a potential association between elevated phosphorylated RAB10 (PRAB10) levels and worse PD severity. This research will advance the mechanistic understanding of genetic and molecular factors underlying familial and idiopathic Parkinson's disease and related neurodegenerative conditions, with potential implications for biomarker development and therapeutic target identification in support of NINDS's mission to reduce the burden of neurological disease across all populations.