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Effects of age, BMI and sex on the glial cell marker TSPO - A multicentre [C]PBR28 HRRT PET study

bioRxiv, ISSN: 2692-8205
2019
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Article Description

Purpose: To investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C]PBR28. Methods: [C]PBR28 data from 140 healthy volunteers (72 males and 68 females; n=78 with HAB and n=62 MAB genotype; age range 19-80 years; BMI range 17.6 - 36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (n=53), Turku PET centre (n=62) and Yale University PET Center (n=25). The total volume of distribution (VT) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results: There were significant positive correlations between age and VT in the frontal and temporal cortex. BMI showed a significant negative correlation with VT in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher VT. A subgroup analysis revealed a positive correlation between VT and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion: These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.

Bibliographic Details

Jouni Tuisku; Laura Airas; Haidar Al-Abdulrasul; Anna Brück; Laura Ekblad; Semi Helin; Noora Lindgren; Päivi Marjamäki; Eero Rissanen; Marcus Sucksdorff; Juha Rinne; Jarkko Johansson; Pontus Plavén-Sigray; Lars Farde; Anton Forsberg; Christer Halldin; Andrea Varrone; Simon Cervenka; Karin Collste; Caroline O. Höglund; Aurelija Jucaite; Per Stenkrona; Mats Lekander; Edward C. Gaiser; Richard E. Carson; Ming Kai Chen; Kelly P. Cosgrove; Irina Esterlis; David Matuskey; Jean Dominique Gallezot; Ansel Hillmer; Yiyun Huang; Nabeel Nabulsi; Christine M. Sandiego; Brian Pittman; Eva Kosek; Jon Lampa

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

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