1. Early Detection of Cerebral Glucose Uptake Changes in the 5XFAD Mouse
- Author
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George Andrew Reid, Ian R. Macdonald, Chris V. Bowen, Sultan Darvesh, Drew R. DeBay, Timothy P. O'Leary, Steven Burrell, George Mawko, Richard E. Brown, Courtney T Jollymore, and Earl Martin
- Subjects
Male ,medicine.medical_specialty ,Pathology ,positron emission tomography ,Tomography Scanners, X-Ray Computed ,Glucose uptake ,glucose metabolism ,Mice, Transgenic ,Plaque, Amyloid ,Carbohydrate metabolism ,Biology ,Presenilin ,Article ,Amyloid beta-Protein Precursor ,Mice ,Alzheimer Disease ,Fluorodeoxyglucose F18 ,Internal medicine ,medicine ,Presenilin-1 ,magnetic resonance imaging ,Animals ,Humans ,Cerebral Cortex ,Tg6799 ,Amyloid beta-Peptides ,medicine.diagnostic_test ,β-amyloid ,Amyloidosis ,Age Factors ,Brain ,computed tomography ,Alzheimer's disease ,medicine.disease ,Disease Models, Animal ,medicine.anatomical_structure ,Endocrinology ,Glucose ,Neurology ,Cerebral cortex ,Positron emission tomography ,Positron-Emission Tomography ,standardized uptake value ,Mutation ,Biomarker (medicine) ,Female ,Neurology (clinical) - Abstract
Brain glucose hypometabolism has been observed in Alzheimer’s disease (AD) patients, and is detected with 18 F 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 18 FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain 18 FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain 18 FDG 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 18 FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.
- Published
- 2014