Longitudinal clinical and biomarker characteristics of non-manifesting LRRK2 G2019S carriers: The PPMI cohort

Autor: Tanya Simuni, Kalpana Merchant, Michael Brumm, Hyunkeun Cho, Chelsea Caspell-Garcia, Chris Coffey, Lana Chahine, Roy Alcalay, Kelly Nudelman, Tatiana Foroud, Brit Mollenhauer, Andrew Siderowf, Caroline Tanner, Hirotaka Iwaki, Todd Sherer, Ken Marek
Rok vydání: 2022
Popis: Background: We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). Methods: We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive motor and non-motor scales, dopamine transporter (DAT) imaging and biofluid biomarkers. The latter included cerebrospinal fluid (CSF) Abeta, total tau and phospho-tau; serum urate and neurofilament light chain (NfL); and urine bis(monoacylglycerol) phosphate (BMP). Findings: At baseline, LRRK2 G2019S NMCs had a mean (SD) age of 62 (7.7) years and were 56% female. 13% had DAT deficit (defined as LRRK2 NMCs developed PD during the follow up. Interpretation: We observed no significant longitudinal change in clinical or biomarker measures in LRRK2 G2019S NMCs in this large, well-characterized cohort. Longer follow up and further selection of NMCs at highest risk for conversion is required for future prevention clinical trials.
Databáze: OpenAIRE