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

Abstract

Alzheimer's disease (AD), the most common age-related neurodegenerative disorder, is characterized by the invariant cerebral accumulation of β-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.

• Authors: Géraldine Poisnel, Anne-Sophie Hérard, Nadine El Tannir El Tayara, Emmanuel Bourrin, Andreas Volk, Frank Kober, Benoit Delatour, Thierry Delzescaux, Thomas Debeir, Thomas Rooney, Jésus Benavides, Philippe Hantraye, Marc Dhenain
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 33 Issue 9 Pg. 1995-2005 (Sep 2012) ISSN: 1558-1497 [Electronic] United States
• PMID: 22079157 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Aif1 protein, mouse
• Amyloid beta-Protein Precursor
• Calcium-Binding Proteins
• Glial Fibrillary Acidic Protein
• Microfilament Proteins
• PSEN1 protein, human
• Presenilin-1
• Fluorodeoxyglucose F18
• Glucose

Topics

• Alzheimer Disease (diagnostic imaging, genetics, pathology)
• Amyloid beta-Protein Precursor (genetics)
• Analysis of Variance
• Animals
• Calcium-Binding Proteins (metabolism)
• Cerebral Cortex (diagnostic imaging, metabolism, pathology)
• Cerebrovascular Circulation (genetics, physiology)
• Disease Models, Animal
• Fluorodeoxyglucose F18
• Glial Fibrillary Acidic Protein (metabolism)
• Glucose (metabolism)
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Microfilament Proteins (metabolism)
• Positron-Emission Tomography
• Presenilin-1 (genetics)