Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To systematically examine the evidence of striatal molecular alterations in premanifest and manifest Huntington’s disease gene expansion carriers (HDGECs) as measured by Positron emission tomography (PET) imaging studies.
Background: There is an urgent need to identify biomarkers able to monitor disease progression and assess the development and efficacy of novel disease-modifying therapies in HD. PET molecular imaging is a powerful tool for detecting molecular alterations in the brains of HDGECs.
Methods: MEDLINE, ISI Web of Science, Cochrane Library and Scopus electronic databases were searched for articles published until 23th November 2015 and included PET studies in premanifest and manifest HDGECs. PET binding in the striatum, caudate, and putamen, as well as demographic, clinical, and methodological variables, were extracted from each publication. PET ligands in premanifest and manifest HDGECs were compared with healthy controls and calculated as mean difference using Comprehensive Meta-Analysis software. Publication bias was assessed with funnel plots and Egger’s intercept. Heterogeneity was addressed with I2 index. Meta-regression analysis was performed to test age, gender, disease duration, CAG repeat, and quality of the study.
Results: Twenty PET studies investigating striatal dopamine, glucose metabolism, microglial activation and phosphodiesterase 10A (PDE10A) levels in manifest (n=191), premanifest (n=158) HDGECs and healthy controls (n=333) were included in a quantitative meta-analysis. In manifest and premanifest HDGECs, the largest mean differences were observed in striatal PDE10A and dopamine D2 receptor levels. Manifest HDGECs showed also significant decreases in striatal dopamine D1 receptor levels and glucose metabolism. Modest changes were found in striatal glucose metabolism and microglial activation in premanifest HDGECs.
Conclusions: The data suggest that decreases in striatal PDE10A and dopamine D2 receptor levels are the strongest molecular changes in both manifest and premanifest HDGECs according to the PET studies conducted to date. Despite 20 years of PET research in HDGECs, conclusions are limited and further studies are needed for building a signature of PET biomarkers across the stages of HD that could monitor disease progression and used as pharmacodynamic measures in therapeutic trials.
To cite this abstract in AMA style:F. Niccolini, G. Pagano, P. Fusar-Poli, A. Wood, L. Mrzljak, C. Sampaio, M. Politis. Striatal molecular alterations in Huntington’s disease gene expansion carriers: A systematic review and meta-analysis of PET studies [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/striatal-molecular-alterations-in-huntingtons-disease-gene-expansion-carriers-a-systematic-review-and-meta-analysis-of-pet-studies/. Accessed September 25, 2023.
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