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

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

Volume: 11 Issue: 5

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 and S. Darvesh

Affiliation:

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

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.

Cite this article as:

Macdonald I.R., DeBay D.R., Reid G.A., O’Leary T.P., Jollymore C.T., Mawko G., Burrell S., Martin E., Bowen C.V., Brown R.E. and Darvesh S., Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse, Current Alzheimer Research 2014; 11 (5) . https://dx.doi.org/10.2174/1567205011666140505111354