Niccolini, F;
Mencacci, NE;
Yousaf, T;
Rabiner, EA;
Salpietro, V;
Pagano, G;
Balint, B;
... Politis, M; + view all
(2018)
PDE10A and ADCY5 mutations linked to molecular and microstructural basal ganglia pathology.
Movement Disorders
10.1002/mds.27523.
(In press).
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Bhatia_PDE10A and ADCY5 mutations linked to molecular and microstructural basal ganglia pathology_VoR.pdf - Published Version Access restricted to UCL open access staff Download (357kB) |
Abstract
BACKGROUND: Striatal cyclic adenosine monophosphate activity modulates movement and is determined from the balance between its synthesis by adenylate cyclase 5 (ADCY5) and its degradation by phosphodiesterase 10A (PDE10A). OBJECTIVE: We assessed the integrity of striatocortical pathways, in vivo, in 2 genetic hyperkinetic disorders caused by ADCY5 and PDE10A mutations. METHODS: We studied 6 subjects with PDE10A and ADCY5 mutations using [11 C]IMA107 PET, [123 I]FP-CIT Single-photon emission computed tomography (SPECT) and multimodal MRI to investigate PDE10A and dopamine transporter availability, neuromelanin-containing neurons, and microstructural white and gray matter changes, respectively. RESULTS: We found that PDE10A and ADCY5 mutations were associated with decreased PDE10A expression in the striatum and globus pallidus, decreased dopamine transporter expression in the striatum, loss of substantia nigra neuromelanin-containing neurons, and microstructural white and gray matter changes within the substantia nigra, striatum, thalamus, and frontoparietal cortices. CONCLUSIONS: Our findings indicate an association between PDE10A and ADCY5 mutations and pre/postsynaptic molecular changes, substantia nigra damage, and white and gray matter changes within the striatocortical pathways.
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