Increased regional cerebral glucose uptake in an APP/PS1 model of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:33

Article

Poisnel, Geraldine^2,3,4  Herard, Anne-Sophie²  El Tayara, Nadine El Tannir^5,6  Bourrin, Emmanuel^2,4  Volk, Andreas^5,6  Kober, Frank⁷  Delatour, Benoit^8,9,10  Delzescaux, Thierry²  Debeir, Thomas³  Rooney, Thomas³  Benavides, Jesus³  Hantraye, Philippe²  Dhenain, Marc^1,2 

[1] CEA, CNRS, MIRCen, URA 2210, F-92265 Fontenay Aux Roses, France

[2] CEA, I2BM, MIRCen, F-92265 Fontenay Aux Roses, France

[3] Alzheimer Parkinson Stroke, Therapeut Strateg Unit Aging, Chilly Mazarin, France

[4] Servier Res Inst, Div Neurodegenerat Dis, Croissy Sur Seine, France

[5] Ctr Univ Orsay, INSERM, U759, Lab 112, F-91405 Orsay, France

[6] Ctr Univ Orsay, Inst Curie, Lab 112, F-91405 Orsay, France

[7] Univ Mediterranee, Fac Med, CNRS, CRMBM,UMR 6612, Marseille, France

[8] CNRS, UMR 7225, Paris, France

[9] INSERM, U975, Paris, France

[10] Univ Paris 06, Fac Med, CRICM, UMR S975, Paris, France

关键词: Alzheimer;    Amyloid;    APP/PS1 transgenic mice;    Biomarker;    Cerebral glucose uptake;    [14C]-2-deoxyglucose;    [18F]-FDG-PET;   

DOI  :  10.1016/j.neurobiolaging.2011.09.026

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of beta-amyloid peptide. This event occurs early in the disease process. In humans, [18F]-fluoro-2-deoxy-D-glucose ([18F]-FDG) positron emission tomography (PET) is largely used to follow-up in vivo cerebral glucose utilization (CGU) and brain metabolism modifications associated with the Alzheimer's disease pathology. Here, [18F]-FDG positron emission tomography was used to study age-related changes of cerebral glucose utilization under resting conditions in 3-, 6-, and 12-month-old APP(SweLon)/PS1(M146L), a mouse model of amyloidosis. We showed an age-dependent increase of glucose uptake in several brain regions of APP/PS1 mice but not in control animals and a higher [18F]-FDG uptake in the cortex and the hippocampus of 12-month-old APP/PS1 mice as compared with age-matched control mice. We then developed a method of 3-D microscopic autoradiography to evaluate glucose uptake at the level of amyloid plaques and showed an increased glucose uptake close to the plaques rather than in amyloid-free cerebral tissues. These data suggest a macroscopic and microscopic reorganization of glucose uptake in relation to cerebral amyloidosis. (C) 2012 Elsevier Inc. All rights reserved.

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