Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse

Author(s): I.R. Macdonald, D.R. DeBay, G.A. Reid, T.P. O’Leary, C.T. Jollymore, G. Mawko, S. Burrell, E. Martin, C.V. Bowen, R.E. Brown, S. Darvesh.

Journal Name:Current Alzheimer Research

Volume 11 , Issue 5 , 2014

Abstract:

Brain glucose hypometabolism has been observed in Alzheimer’s disease (AD) patients, and is detected with 18F radiolabelled glucose, using positron emission tomography. A pathological hallmark of AD is deposition of brain β- amyloid plaques that may influence cerebral glucose metabolism. The five times familial AD (5XFAD) mouse is a model of brain amyloidosis exhibiting AD-like phenotypes. This study examines brain β-amyloid plaque deposition and 18FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain 18FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain 18FDG uptake at 13 months relative to wild-type controls but not in younger mice, despite substantial β- amyloid plaque deposition. However, by comparing the ratio of uptake values for glucose in different regions in the same brain, 5XFAD mice could be distinguished from controls at age 2 months. This method of measuring altered glucose metabolism may represent an early biomarker for the progression of amyloid deposition in the brain. We conclude that brain 18FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.

Keywords: Alzheimer's disease, β-amyloid, computed tomography, glucose metabolism, magnetic resonance imaging, positron emission tomography, standardized uptake value, Tg6799.

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Article Details

VOLUME: 11
ISSUE: 5
Year: 2014
Page: [450 - 460]
Pages: 11
DOI: 10.2174/1567205011666140505111354