Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice.
BACKGROUND
Early diagnosis assumes a vital role in an effective treatment of Alzheimer's disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.


METHODS
A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(18F) fluoro-D-glucose ([18F]-FDG) uptake in the hippocampus and cerebral cortex.


RESULTS
With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (18F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (18F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared.


CONCLUSIONS
The decline of (18F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.
Nai-An
NA
Xiao
Jing
J
Zhang
Meng
M
Zhou
Zhen
Z
Wei
Xi-Lin
XL
Wu
Xiao-Man
XM
Dai
Yuan-Gui
YG
Zhu
Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Affiliated Union Hospital of Fujian Medical University; Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
Xiao-Chun
XC
Chen
D000544:Alzheimer Disease / Q000175:diagnosis*; D000682:Amyloid / Q000032:analysis; D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers / Q000032:analysis*; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D009830:Olfactory Bulb / Q000378:metabolism*; D049268:Positron-Emission Tomography
D000682:Amyloid; D015415:Biomarkers; D019788:Fluorodeoxyglucose F18; D005947:Glucose