Τρίτη 15 Ιανουαρίου 2019

Longitudinal association between astrocyte function and glucose metabolism in autosomal dominant Alzheimer’s disease

Abstract

Purpose

The spatial resolution of 18F-fluorodeoxyglucose PET does not allow the specific cellular origin of its signal to be determined, but it is commonly accepted that transport and trapping of 18F-fluorodeoxyglucose reflects neuronal glucose metabolism. The main frameworks for the diagnosis of Alzheimer's disease suggest that hypometabolism measured with 18F-fluorodeoxyglucose PET is a biomarker of neuronal injury and neurodegeneration. There is preclinical evidence to suggest that astrocytes contribute, at least partially, to the in vivo 18F-fluorodeoxyglucose PET signal. However, due to a paucity of PET tracers for imaging astrocytic processes, the relationship between astrocyte function and glucose metabolism in human brain is not fully understood. The aim of this study was to investigate the longitudinal association between astrocyte function and glucose metabolism in Alzheimer's disease.

Methods

The current investigation combined longitudinal PET data from patients with autosomal dominant Alzheimer's disease, including data on astrocyte function (11C-deuterium-l-deprenyl binding) and glucose metabolism (18F-fluorodeoxyglucose uptake). Research participants included 7 presymptomatic and 4 symptomatic mutation carriers (age 44.9 ± 9.8 years and 58.0 ± 3.7 years, respectively) and 16 noncarriers (age 51.1 ± 14.2 years). Eight carriers and eight noncarriers underwent longitudinal follow-up PET imaging at an average of 2.8 ± 0.2 and 3.0 ± 0.5 years from baseline, respectively.

Results

Longitudinal decline in astrocyte function as measured using 11C-deuterium-l-deprenyl PET was significantly associated with progressive hypometabolism (18F-fluorodeoxyglucose uptake) in mutation carriers; no significant association was observed in noncarriers.

Conclusion

The emerging data shift the accepted wisdom that decreases in cerebral metabolism measured with 18F-fluorodeoxyglucose solely reflect neuronal injury, and places astrocytes more centrally in the development of Alzheimer's disease.



from #Head and Neck by Sfakianakis via simeraentaxei on Inoreader http://bit.ly/2VXL9Z1

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