EXPRESS: Longitudinal FDG-PET reveals early hypermetabolism associated with astrocyte changes in TgF344-AD rats
BACKGROUND: Alzheimer's disease (AD) is characterized by alterations in brain glucose metabolism, classically showing [18F]FDG-PET hypometabolism in later stages. However, emerging evidence suggests a transient phase of glucose hypermetabolism early in the disease, for which biological basis remains unclear. METHODS: F]FDG-microPET imaging, behavioral testing, and cerebrospinal fluid biomarker analysis. Cross-sectional analyses included amyloid histopathology, western blot and ex vivo glutamate uptake measurements. RESULTS: TgF344-AD rats exhibited increased cerebral glucose metabolism at 9mo, predominantly in cortical regions. This phase coincided with emerging cognitive impairment and early amyloid deposition. CSF analyses showed increased GFAP at 9-12mo and reduced S100B at 9mo, while microglial/inflammatory markers remained unchanged. WB confirmed region-specific GFAP alterations without changes in neuronal or synaptic markers. Glutamate uptake was increased in the cortex and hippocampus at 9mo. CONCLUSION: These findings identify a transient phase of increased glucose metabolism early in disease progression, associated with astrocyte-related changes, suggesting that early hypermetabolism may reflect non-neuronal processes. This has implications for the interpretation of [18F]FDG-PET as a biomarker in early AD and for understanding early physiological responses to AD pathology.
Authors
- J C da Costa (ORCID: https://orcid.org/0000-0001-6776-1515)
- Tharick Ali Pascoal (ORCID: https://orcid.org/0000-0001-9057-8014)
- Eduardo Rigon Zimmer (ORCID: https://orcid.org/0000-0002-5349-0053)
- Gianina Teribele Venturin (ORCID: https://orcid.org/0000-0001-7696-8219)
- Luiza Santos Machado (ORCID: https://orcid.org/0000-0001-8387-3832)
- Gabriela Lazzarotto (ORCID: https://orcid.org/0000-0001-8035-3639)
- Stefânia Forner (ORCID: https://orcid.org/0000-0001-7977-4866)
- Pâmela C.L. Ferreira (ORCID: https://orcid.org/0000-0003-2134-9829)
- Peter Kunach (ORCID: https://orcid.org/0000-0001-7428-6812)
- Bruna Bellaver (ORCID: https://orcid.org/0000-0002-2212-3373)
- Samuel Greggio (ORCID: https://orcid.org/0000-0002-5187-0335)
- Giedre Milinkeviciute (ORCID: https://orcid.org/0000-0003-2527-3892)
- Andréia Silva da Rocha (ORCID: https://orcid.org/0000-0003-1567-3374)
- Diogo Onofre Souza (ORCID: https://orcid.org/0000-0002-4322-0404)
- Pedro Rosa‐Neto (ORCID: https://orcid.org/0000-0001-9116-1376)
- Pedro Rodrigues Vidor (ORCID: https://orcid.org/0000-0001-9208-7323)
- Kim Green
- Carolina Soares
- Fernanda Bastos de Mello
- Patricia Carvalho
Institutions
- Universidade Federal do Rio Grande do Sul (BR)
- University of Pittsburgh (US)
- University of California, Irvine (US)
- Instituto do Cérebro (BR)
- Pontifícia Universidade Católica do Rio Grande do Sul (BR)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Journal of Cerebral Blood Flow & Metabolism
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1177/0271678x261504653
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00