Regional cerebral glucose uptake in the 3xTG model of Alzheimer's disease highlights common regional vulnerability across AD mouse models
Open accessAbstract
We have previously used fluorodeoxyglucose (FDG) autoradiography to detect the pattern of metabolic declines in two different transgenic mouse models of fibrillar beta-amyloid pathology in Alzheimer's disease (AD), including the PDAPP mouse, which overexpresses a mutant form of human APP, and the PSAPP mouse, which overexpresses mutant forms of the human APP and PS1 genes. In this study, we used the same approach to study a triple-transgenic (3xTG) model of AD, which overexpresses human APP, PS1 and tau mutations, and progressively develops amyloid plaques, neurofibrillary tangles, and synaptic dysfunction. Densitometric measurements from 55 brain regions were characterized and compared in 2, 12, and 18 month-old 3xTG and wildtype control mice (n = 12/group). By 18 months of age, the 3xTG mice had significant reductions in FDG uptake in every measured brain region, including cortical and subcortical gray matter, cerebellar and brainstem regions. However, regional differences in normalized FDG uptake were apparent in the 2- and 12-month-old 3xTG mice, in a brain network pattern reminiscent of our previous analyses in the other mouse models. This prominently included the posterior cingulate/retrosplenial cortex, as in each previously-analyzed model. Overall, our analyses highlight consistencies in brain glucose uptake abnormalities across multiple mouse models of amyloid-associated pathophysiology. These mouse brain regional changes are homologous to alterations seen in PET scans from human AD patients and could thus be useful biomarkers for early testing of novel interventions.
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In mice, the somatosensory cortex appears as metabolically active as the cingulate.
“the somatosensory cortex appears as metabolically active as the cingulate in mice (Nicholson et al., 2010).”
From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Nicholson et al., 2010
The Results and Discussion report glucose-uptake changes in the posterior cingulate cortex of AD-model mice, but do not compare its metabolic activity with that of the somatosensory cortex. Searches for “somatosensory” and for a comparison of somatosensory and cingulate glucose uptake found no passage addressing the claim. (LLM, conf=0.75)
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“Although, in humans, the DMN is the metabolically most active network in the brain at rest (Raichle et al., 2001), the somatosensory cortex appears as metabolically active as the cingulate in mice (Nicholson et al., 2010).”
BackgroundAlzheimer's disease biomarkers: correspondence between human studies and animal models
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- Authors
- Nicholson, R. M., Kusne, Y., Nowak, L. A., LaFerla, F. M., Reiman, E. M., & Valla, J.
- Affiliations
- Barrow Neurological Institute (US)
- University of California, Irvine (US)
- Translational Genomics Research Institute (US)
- Corresponding author
- Valla, Jon
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 1347
- Pages
- 179-185
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC2974951
- OpenAlex
- W2002306490
- Cited by
- 107
- References
- 5
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 4 · 2014: 11 · 2013: 12 · 2012: 10
- FWCI
- 6.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (P30AG019610)
- 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, 3xTg mouse model, amyloid-beta, APP overexpression, PS1 mutations, tau mutations, amyloid plaques, neurofibrillary tangles, posterior cingulate cortex, retrosplenial cortex, transgenic mouse model, biomarkers
- MeSH terms
- Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Cerebral Cortex, Disease Models, Animal, Glucose, Humans, Mice, Inbred C57BL, Mice, Transgenic, Radionuclide Imaging, Amyloid beta-Protein Precursor, tau Proteins, Fluorodeoxyglucose F18, Mice, Presenilin-1
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