Session Time: 1:15pm-2:45pm
Location: Les Muses Terrace, Level 3
Objective: We hypothesised that abnormal sprouting of serotonergic terminals in the hypothalamus may lead to abnormal structural connectivity, which can be measured with diffusion tensor imaging (DTI).
Background: In a previous study, Leucine-rich repeat kinase 2 (LRRK2) mutation carriers without manifest Parkinson’s disease (PD) showed increased serotonin transporter binding in the hypothalamus, possibly reflecting compensatory changes preceding the motor onset of PD.
Method: We acquired T1- and DTI-MRI data of 32 LRRK2 mutation carriers, 18 without manifest PD (LRRK2-asymptomatic) and 14 with manifest PD (LRRK2-PD) to assess structural changes in grey (GM) and white matter (WM) in comparison with 36 healthy controls and 116 idiopathic PD patients. Voxel-based morphometry (VBM) was used to quantify GM changes and tract-based spatial statistics to quantify WM fractional anisotropy (FA) and mean diffusivity (MD).
Results: LRRK2-asymptomatic carriers had greater non-motor burden (higher MDS-UPDRS Part-I, P<0.05) compared to healthy controls. LRRK2-asymptomatic showed increased WM FA in the hypothalamus (P<0.05) and reduced WM FA in the thalamus (P<0.05) and globus pallidus (P<0.0001) compared to healthy controls. No differences were found in other areas for GM, WM FA or WM MD.
Conclusion: We found that LRRK2-asymptomatic carriers, a model of premotor PD, had abnormal sprouting of presynaptic terminals at DTI-MRI imaging in the hypothalamus, thalamus and globus pallidus. These imaging changes might be the result of the pathological changes in the premotor stages of PD, however, further studies on prodromal PD may clarify this hypothesis.
To cite this abstract in AMA style:G. Pagano, P. Vickers, J. Schulz, H. Wilson, M. Politis. Structural connectivity changes in G2019S-LRRK2 gene mutation carriers without manifest Parkinson’s disease [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/structural-connectivity-changes-in-g2019s-lrrk2-gene-mutation-carriers-without-manifest-parkinsons-disease/. Accessed December 1, 2023.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-connectivity-changes-in-g2019s-lrrk2-gene-mutation-carriers-without-manifest-parkinsons-disease/