Author:
Crivelli Simone M.,van Kruining Daan,Luo Qian,Stevens Jo A. A.,Giovagnoni Caterina,Paulus Andreas,Bauwens Matthias,Berkes Dusan,de Vries Helga E.,Mulder Monique T.,Walter Jochen,Waelkens Etienne,Derua Rita,Swinnen Johannes V.,Dehairs Jonas,Mottaghy Felix M.,Losen Mario,Bieberich Erhard,Martinez-Martinez Pilar
Abstract
Abstract
The metabolism of ceramides is deregulated in the brain of Alzheimer’s disease (AD) patients and is associated with apolipoprotein (APO) APOE4 and amyloid-β pathology. However, how the ceramide metabolism changes over time in AD, in vivo, remains unknown. Distribution and metabolism of [18F]F-HPA-12, a radio-fluorinated version of the ceramide analog N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide, was investigated in the brain of AD transgenic mouse models (FAD) on an APOE4 or APOE3 genetic background, by positron emission tomography and by gamma counter. We found that FAD mice displayed a higher uptake of [18F]F-HPA-12 in the brain, independently from the APOE4 or APOE3 genetic background. FAD mice could be distinguished from littermate control animals with a sensitivity of 85.7% and a specificity of 87.5%, by gamma counter measurements. Metabolic analysis of [18F]F-HPA-12 in the brain suggested that the tracer is degraded less efficiently in the FAD mice. Furthermore, the radioactive signal registered in the hippocampus correlated with an increase of Cer d18:1/20:2 levels measured in the same brain region by mass spectrometry. Our data gives additional proof that ceramide metabolism is different in FAD mice compared to controls. Ceramide analogs like HPA-12 may function as metabolic probes to study ceramide disbalance in the brain.
Funder
ZonMw
Foundation for the National Institutes of Health
U.S. Department of Veterans Affairs
Alzheimer Nederland
Publisher
Springer Science and Business Media LLC
Cited by
8 articles.
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