title: Early detection of cerebral glucose uptake changes in the 5XFAD mouse.
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.
authors.forename: I R
authors.initials: IR
authors.lastname: Macdonald
authors.forename: D R
authors.initials: DR
authors.lastname: DeBay
authors.forename: G A
authors.initials: GA
authors.lastname: Reid
authors.forename: T P
authors.initials: TP
authors.lastname: O'Leary
authors.forename: C T
authors.initials: CT
authors.lastname: Jollymore
authors.forename: G
authors.initials: G
authors.lastname: Mawko
authors.forename: S
authors.initials: S
authors.lastname: Burrell
authors.forename: E
authors.initials: E
authors.lastname: Martin
authors.forename: C V
authors.initials: CV
authors.lastname: Bowen
authors.forename: R E
authors.initials: RE
authors.lastname: Brown
authors.affiliation: Room 1308, Camp Hill Veterans' Memorial, 5955 Veterans' Memorial Lane, Halifax, Nova Scotia, B3H 2E1. Canada. sultan.darvesh@dal.ca.
authors.forename: S
authors.initials: S
authors.lastname: Darvesh
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography; D053764:Presenilin-1 / Q000235:genetics; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D019788:Fluorodeoxyglucose F18; D005947:Glucose