Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice

Abstract

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-(18 F) fluoro-D-glucose ([18 F]-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 (18 F)-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 (18 F)-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 (18 F)-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.

In vivo Imaging With 18F-FDG- and 18F-Florbetaben-PET/MRI Detects Pathological Changes in the Brain of the Commonly Used 5XFAD Mouse Model of Alzheimer's Disease

“…Macdonald et al ( 12 ) described a significant decrease of 18 F-FDG uptake in 13-month-old 5XFAD mice, while younger animals did not show differences in the whole brain SUV compared to WT. Another study by Xiao et al ( 40 ) reported lower 18 F-FDG uptake in the cerebral cortex, hippocampus and olfactory bulb of 6-month-old 5XFAD mice. Hypometabolism within the olfactory bulb was detected as early as 3 months of age ( 40 ).…”

Alcohol Drinking Exacerbates Neural and Behavioral Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease

“…The widely used 5XFAD mouse line express a total of five human APP and PSEN-1 transgenes, which results in rapid onset of amyloid plaques throughout the cortex and hippocampus as early as two months of age (Oakley et al, 2006) and could, therefore, be used to assess site-specific amyloid pathology associated with alcohol exposure. The 5XFAD mouse line also shows a deficit in spatial memory (Xiao et al, 2015) suggesting that cognitive decline associated with amyloid pathology can be modeled in APP / PSEN-1 transgenic mouse lines.…”

Cerebral Responses to Acupuncture at GV24 and Bilateral GB13 in Rat Models of Alzheimer’s Disease

“…The Papez circuit enables the connection between the cingulate gyrus and hippocampus, and it plays an important role in memory function [ 43 ]. Recently, the hypometabolism of the olfactory bulb has served as a potential marker of the diagnosis of AD and is related to memory deficits [ 44 , 45 ]. Although some studies suggested that A β deposits in this area may promote AD pathology [ 46 , 47 ], another study has found that the deposition of the TAR DNA-binding protein of 43 kDa (TDP-43) in the olfactory bulb was associated with AD and associated symptoms including episodic memory loss and hippocampal atrophy [ 48 , 49 ].…”