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Cited by 112Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Glucose metabolism and AD: evidence for a potential diabetes type 3

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González, Andrea, Calfío, Camila, Churruca, Macarena, Maccioni, Ricardo B.·2022·Alzheimer's Research & Therapy
DOI 10.1186/s13195-022-00996-8PMC PMC9022265
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Abstract

Background: Alzheimer’s disease is the most prevalent cause of dementia in the elderly. Neuronal death and synaptic dysfunctions are considered the main hallmarks of this disease. The latter could be directly associated to an impaired metabolism. In particular, glucose metabolism impairment has demonstrated to be a key regulatory element in the onset and progression of AD, which is why nowadays AD is considered the type 3 diabetes. Methods: We provide a thread regarding the influence of glucose metabolism in AD from three different perspectives: (i) as a regulator of the energy source, (ii) through several metabolic alterations, such as insulin resistance, that modify peripheral signaling pathways that influence activation of the immune system (e.g., insulin resistance, diabetes, etc.), and (iii) as modulators of various key post-translational modifications for protein aggregation, for example, influence on tau hyperphosphorylation and other important modifications, which determine its self-aggregating behavior and hence Alzheimer’s pathogenesis. Conclusions: In this revision, we observed a 3 edge-action in which glucose metabolism impairment is acting in the progression of AD: as blockade of energy source (e.g., mitochondrial dysfunction), through metabolic dysregulation and post-translational modifications in key proteins, such as tau. Therefore, the latter would sustain the current hypothesis that AD is, in fact, the novel diabetes type 3.

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  • FDG-PET imaging has demonstrated markedly reduced glucose uptake in temporoparietal association cortices, posterior cingulate, and hippocampal regions of patients with MCI and early AD, often preceding overt clinical symptoms.

    “FDG-PET imaging has demonstrated markedly reduced glucose uptake in temporoparietal association cortices, the posterior cingulate, and hippocampal regions of patients with mild cognitive impairment (MCI) and early AD, often preceding overt clinical symptoms [67].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [67]

    The Insulin resistance section (page unavailable) associates impaired glucose metabolism with AD and describes FDG-PET as a proposed biomarker of brain carbohydrate metabolism. It does not report FDG-PET findings for the named brain regions in patients with MCI or early AD, or establish that reduced uptake precedes clinical symptoms. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
González, A., Calfío, C., Churruca, M., & Maccioni, R. B.
Affiliations
  • University of Chile (CL)
  • Hospital del Salvador (CL)
Corresponding author
Maccioni, Ricardo B.
ORCID
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2022-04-20
Volume
14
Issue
1
Pages
56-56
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/s13195-022-00996-8
PMC
PMC9022265
OpenAlex
W4224233089
Cited by
112
References
15
Citations by year
2026: 28 · 2025: 29 · 2024: 26 · 2023: 26 · 2022: 3
FWCI
2.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Universidad de Chile (submittedVersion, cc-by-nc-nd)
Funders
Agencia Nacional de Investigación y Desarrollo (i7819020001, ID19I10301)
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, glucose metabolism, type 3 diabetes, insulin resistance, mitochondrial dysfunction, tau hyperphosphorylation, protein aggregation, post-translational modification, synaptic dysfunction, energy metabolism, immune signaling
MeSH terms
Aged, Alzheimer Disease, Diabetes Mellitus, Glucose, Humans, Insulin Resistance, Signal Transduction

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