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Cited by 79Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Macdonald, I.R., DeBay, D.R., Reid, G.A., O’Leary, T.P., Jollymore, C.T., Mawko, G., Burrell, S., Martin, E. +3 more·2014·Current Alzheimer Research
DOI 10.2174/1567205011666140505111354PMC PMC4082185
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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.

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  • Mutations in both APP and PSEN1 cause aberrant APP cleavage and clearance that lead to neuroinflammation, activation of astrocytes and microglia, and changes in bioenergetics.

    “Mutations in both APP and PSEN1 cause aberrant APP cleavage and clearance4,47 that lead to neuroinflammation, the activation of astrocytes and microglia, and changes in bioenergetics44,48.”

    From Magnetic resonance microscopy maps widespread effects of Alzheimer’s disease on brain structures and behavior in mice (2026) · cites this paper as [47]

    The Introduction (page not provided) describes familial-AD mutation mouse models with activated microglia, neuroinflammation, mitochondrial abnormalities, and possible changes in glucose metabolism. It does not mention astrocyte activation, and it presents the metabolic link as a possibility rather than an established consequence. (LLM, conf=0.84)

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Authors
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., & Darvesh, S.
Affiliations
  • Dalhousie University (CA)
  • Mount Saint Vincent University (CA)
Corresponding author
  • Burrell, S.
  • Martin, E.
ORCID
Venue
Current Alzheimer Research
Publisher
Bentham Science Publishers Ltd.
Published
2014-06-12
Volume
11
Issue
5
Pages
450-460
ISSN
1567-2050 (ISSN-L)
DOI
10.2174/1567205011666140505111354
PMC
PMC4082185
OpenAlex
W2147059796
Cited by
79
References
31
Citations by year
2026: 7 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 15 · 2021: 8 · 2020: 8 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 2 · 2014: 1
FWCI
3.33
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Current Alzheimer Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Dalhousie Medical Research Foundation
  • Nova Scotia Health Research Foundation (MED‐MAT‐2011‐7512)
  • Dalhousie University
  • Canadian Institutes of Health Research (RNS- 117795, 119343_1)
  • Natural Sciences and Engineering Research Council of Canada (A7441)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, brain glucose hypometabolism, FDG uptake, amyloid plaques, amyloid deposition, early biomarkers, brain glucose metabolism, transgenic mouse model
MeSH terms
Age Factors, Alzheimer Disease, Animals, Brain, Cerebral Cortex, Disease Models, Animal, Female, Glucose, Humans, Magnetic Resonance Imaging, Male, Mice, Transgenic, Mutation, Tomography Scanners, X-Ray Computed, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Fluorodeoxyglucose F18, Positron-Emission Tomography, Mice, Presenilin-1, Plaque, Amyloid

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