The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
Insulin Resistance as Common Molecular Denominator Linking Obesity to Alzheimer‘s Disease
Abstract
Alzheimer's disease (AD) is an aging-related multi-factorial disorder to which metabolic factors contribute at what has canonically been considered a centrally mediated process. Although the exact underlying mechanisms are still unknown, obesity is recognized as a risk factor for AD and the condition of insulin resistance seems to be the link between the two pathologies. Using mice with high fat diet (HFD) obesity we dissected the molecular mechanisms shared by the two disorders. Brains of HFD fed mice showed elevated levels of APP and Aβ40/Aβ42 together with BACE, GSK3β and Tau proteins involved in APP processing and Aβ accumulation. Immunofluorescence, Thioflavin T staining experiments, confirmed increased Aβ generation, deposition in insoluble fraction and plaques formation in both the hippocampus and the cerebral cortex of HFD mice. Presence of Aβ40/Aβ42 in the insoluble fraction was also shown by ELISA assay. Brain insulin resistance was demonstrated by reduced presence of insulin receptor (IRs) and defects in Akt-Foxo3a insulin signaling. We found reduced levels of phospho-Akt and increased levels of Foxo3a in the nuclei of neurons where proapototic genes were activated. Dysregulation of different genes related to insulin resistance, especially those involved in inflammation and adipocytokines synthesis were analyzed by Profiler PCR array. Further, HFD induced oxidative stress, mitochondrial dysfunction and dynamics as demonstrated by expression of biomarkers involved in these processes. Here, we provide evidence that obesity and AD markers besides insulin resistance are associated with inflammation, adipokine dyshomeostasis, oxidative stress and mitochondrial dysfunction, all mechanisms leading to neurodegeneration.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“A recent study showed that insulin resistance secondary to a high-fat diet leads to increased levels of oxidative stress, which contributes to neurodegeneration in AD [44].”
From Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin (2017) · cites this paper as [44]
Citations
Cites
Adipose Tissue as an Endocrine Organ
Kershaw, E. E., & Flier, J. S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0395 · Cited by 5,522
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
Diabetes mellitus and the risk of dementia: The Rotterdam Study
Ott, A., Stolk, R. P., van Harskamp, F., Pols, H. A. P., Hofman, A., & Breteler, M. M. B. (1999) · Neurology · doi:10.1212/wnl.53.9.1937 · Cited by 2,175
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703
Craft, S. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.233 · Cited by 1,253
Impaired Balance of Mitochondrial Fission and Fusion in Alzheimer's Disease
Wang, X., Su, B., Lee, H.-G., Li, X., Perry, G., Smith, M. A., & Zhu, X. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1357-09.2009 · Cited by 1,224
Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., & Gómez‐Pinilla, F. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00123-9 · Cited by 918
Cited by
Sorted by citations
An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus
Heydemann, A. (2016) · Journal of Diabetes Research · doi:10.1155/2016/2902351 · Cited by 392
Therapies for Prevention and Treatment of Alzheimer’s Disease
Mendiola-Precoma, J., Berumen, L. C., Padilla, K., & García‐Alcocer, G. (2016) · BioMed Research International · doi:10.1155/2016/2589276 · Cited by 262
Spinelli, M., Fusco, S., Mainardi, M., Scala, F., Natale, F., Lapenta, R., Mattera, A., Rinaudo, M., Puma, D. D. L., Ripoli, C., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02221-9 · Cited by 213
Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease
Al-Ghraiybah, N. F., Wang, J., Alkhalifa, A. E., Roberts, A. B., Raj, R., Yang, E., & Kaddoumi, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810572 · Cited by 217
Sripetchwandee, J., Chattipakorn, N., & Chattipakorn, S. C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00496 · Cited by 199
Metadata
- Authors
- Nuzzo, D., Picone, P., Baldassano, S., Caruana, L., Messina, E., Gammazza, A., Cappello, F., Mulè, F., & Carlo, M.
- Affiliations
- National Research Council (IT)
- Istituto di Biomedicina e di Immunologia Molecolare Alberto Monroy (IT)
- ORCID
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2015-09-11
- Volume
- 12
- Issue
- 8
- Pages
- 723-735
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W831032665
- Cited by
- 119
- References
- 60
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 9 · 2023: 9 · 2022: 11 · 2021: 6 · 2020: 13 · 2019: 19 · 2018: 15 · 2017: 10 · 2016: 16 · 2015: 1
- FWCI
- 10.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- insulin resistance, Alzheimer's disease, obesity, high-fat diet, amyloid-beta, APP processing, BACE, GSK3β, tau protein, insulin receptor, neuroinflammation, adipokines, oxidative stress, mitochondrial dysfunction, neurodegeneration, amyloid plaques
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Gene Expression Regulation, Insulin, Insulin Resistance, Male, Mice, Inbred C57BL, Obesity, Receptor, Insulin, Time Factors, Signal Transduction, Case-Control Studies, Cytokines, Oxidative Stress, Glycogen Synthase Kinase 3, Mice, Amyloid Precursor Protein Secretases, Amyloidogenic Proteins, Diet, High-Fat
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
