Objective: To investigate SN Neuromelanin in asymptomatic LRRK2 carriers.

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder with long pre-clinical and prodromal stages. The development of non-invasive biomarkers for pre-diagnostic stages is of utmost importance. Neuromelanin (NM)-sensitive magnetic resonance imaging (MRI) of the substantia nigra (SN) is an established biomarker of neurodegeneration in PD, which is expected to begin years before motor symptoms emerge, and for which LRRK2 mutation asymptomatic carriers are at higher risk.

Method: Asymptomatic at-risk first-degree relatives of LRRK2-PD patients were sequentially recruited. An extensive clinical evaluation, including motor and non-motor symptoms, as well as a study of NM using a specific T1-weighted MRI sequence, were performed. Targeted genetic testing for LRRK2 variants was performed after clinical evaluation and imaging studies.

Results: Nineteen asymptomatic participants were included, of which – 12 LRRK2 non-carriers (NC) and 7 carriers (AC). Baseline demographics did not differ between groups (median age AC 46 years (IQR 35-53) vs NC 51.5 (39-59) p=0.379). Motor scores did not differ between groups (MDS-UPDRS III median 2 (2-4) in AC vs 2.5 (1.5-5-4) in NC, p=0.863). NM area was significantly smaller in AC when compared to NC, (16 mm²(14.9-19.1) vs 20.6 mm²(19.3-24.0), p=0.025).

Conclusion: NM-MRI can be significantly decreased in LRRK2-G2019S AC. This technique might be a promising biomarker of neurodegeneration in pre-diagnostic stages of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/substantia-nigra-neuromelanin-magnetic-resonance-imaging-in-lrrk2-asymptomatic-carriers/