The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Limited Alzheimer-Type Neurodegeneration in Experimental Obesity and Type 2 Diabetes Mellitus
Open accessAbstract
Alzheimer's disease (AD) is associated with brain insulin resistance and insulin deficiency, whereas Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance. This study assesses the degree to which T2DM causes AD-type neurodegeneration. In a C57BL/6 mouse model of obesity and T2DM, we characterized the histopathology, gene expression, and insulin and insulin-like growth factor (IGF)-receptor binding in temporal lobe. High fat diet (HFD) feeding for 16 weeks doubled mean body weight, caused T2DM, and marginally reduced mean brain weight. These effects were associated with significantly increased levels of tau, IGF-I receptor, insulin receptor substrate-1 (IRS-1), IRS-4, ubiquitin, glial fibrillary acidic protein, and 4-hydroxynonenol, and decreased expression of beta-actin. HFD feeding also caused brain insulin resistance manifested by reduced BMAX for insulin receptor binding, and modestly increased brain insulin gene expression. However, HFD-fed mouse brains did not exhibit AD histopathology, increases in amyloid-beta or phospho-tau, or impairments in IGF signaling or acetylcholine homeostasis. Obesity and T2DM cause brain atrophy with insulin resistance, oxidative stress, and cytoskeleton degradation, but the absence of many features that typify AD suggests that obesity and T2DM may contribute to, but are not sufficient to cause AD.
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“Recent evidence suggests that insulin resistance, a hallmark of diabetes, develops in Alzheimer’s brains (, 2000; Craft et al., 1999; de la Monte, 2009; Moroz et al., 2008; Pedersen and Flynn, 2004; Razay and Wilcock, 1994; Watson and Craft, 2003).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Moroz et al., 2008
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Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
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
Increased Risk of Type 2 Diabetes in Alzheimer Disease
Janson, J., Laedtke, T., Parisi, J. E., O’Brien, P., Petersen, R. C., & Butler, P. C. (2004) · Diabetes · doi:10.2337/diabetes.53.2.474 · Cited by 950
Intranasal insulin improves cognition and modulates β-amyloid in early AD
Reger, M. A., Watson, G. S., Green, P. S., Wilkinson, C. W., Baker, L. D., Cholerton, B., Fishel, M. A., Plymate, S. R., Breitner, J. C. S., DeGroodt, W., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000265401.62434.36 · Cited by 830
Aggregation of vascular risk factors and risk of incident Alzheimer disease
Luchsinger, J. A., Reitz, C., Honig, L. S., Tang, M. X., Shea, S., & Mayeux, R. (2005) · Neurology · doi:10.1212/01.wnl.0000172914.08967.dc · Cited by 790
Adipokines: The missing link between insulin resistance and obesity
Antuna-Puente, B., Fève, B., Fellahi, S., & Bastard, J. (2008) · Diabetes & Metabolism · doi:10.1016/j.diabet.2007.09.004 · Cited by 760
Rivera, E. J., Goldin, A., Fulmer, N., Tavares, R., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8304 · Cited by 723 · cited 5×
“…A β PP gene expression; 4) pro-inflammatory cytokine activation; 5) impairments in IGF-I and IGF-II receptor binding; 6) reduced expression of IGF-I and IGF-II polypeptide and receptor genes;and 7) impairments in acetylcholine homeostasis [14,32,50,56] were not present in ourmod-el of obesity/T2DM.”
InfluentialIntranasal insulin improves memory in humans
Benedict, C., Hallschmid, M., Hatke, A., Schultes, B., Fehm, H. L., Born, J., & Kern, W. (2004) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2004.04.003 · Cited by 699
Reger, M. A., Watson, G. S., Frey, W. H., Baker, L. D., Cholerton, B., Keeling, M. L., Belongia, D., Fishel, M. A., Plymate, S. R., Schellenberg, G. D., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.016 · Cited by 619
Relation of diabetes to mild cognitive impairment
Luchsinger, J. A., Reitz, C., Patel, B., Tang, M.-X., Manly, J. J., & Mayeux, R. (2007) · Archives of Neurology · doi:10.1001/archneur.64.4.570 · Cited by 592
Cited by
Sorted by citations
Alzheimer’s disease is type 3 diabetes—Evidence reviewed
de la Monte, S. M., & Wands, J. R. (2008) · Journal of Diabetes Science and Technology · doi:10.1177/193229680800200619 · Cited by 1,158
Obesity and neuroinflammation: A pathway to cognitive impairment
Miller, A. A., & Spencer, S. J. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.04.001 · Cited by 834
Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
Mehran, A. E., Templeman, N. M., Brigidi, G. S., Lim, G. E., Chu, K.-Y., Hu, X., Botezelli, J. D., Asadi, A., Hoffman, B. G., Kieffer, T. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.019 · Cited by 498
Brain metabolic dysfunction at the core of Alzheimer's disease
de la Monte, S. M., & Tong, M. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.012 · Cited by 472
“Correspondingly, experimental diet-induced obesity and T2DM cause cognitive declines [35] with deficits in spatial learning and memory [120], and brain atrophy with insulin resistance, inflammation, oxidative stress, and cholinergic dysfunction [111, 121].”
BackgroundBrain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimers Disease
de la Monte, S. M. (2012) · Current Alzheimer Research · doi:10.2174/156720512799015037 · Cited by 468
“With experimental steatohepatitis caused by DIO or low-level nitrosamine exposure, hepatic and peripheral insulin resistance are also accompanied by locally and peripherally increased ceramide levels [22, 83, 105, 123, 124].”
Background
Metadata
- Authors
- Moroz, N., Tong, M., Longato, L., Xu, H., & de la Monte, S. M.
- Affiliations
- Brown University (US)
- Departments of Medicine, Pathology, and Clinical Neuroscience, Divisions of Gastroenterology and Endocrinology, and the Liver Research Center, Rhode Island Hospital and the Warren Alpert Medical School of Brown University, Providence, RI, USA
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2008-08-26
- Volume
- 15
- Issue
- 1
- Pages
- 29-44
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC10074393
- OpenAlex
- W157753509
- Cited by
- 151
- References
- 71
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 10 · 2023: 2 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 4 · 2018: 9 · 2017: 4 · 2016: 8 · 2015: 9 · 2014: 11 · 2013: 14 · 2012: 17
- FWCI
- 7.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Charles H. Hood Foundation
- National Institute for Health and Care Research
- National Institutes of Health (AA-02169, AA02666, AA-11431, 5r01aa011431-26)
- National Institute on Alcohol Abuse and Alcoholism (AA-02666, R01-AA011431, K24 AA016126, AA-12908, AA-02169, AA-16126, AA11431, R56AA011431, R01AA012908, R37AA002666, R37AA011431, R01AA002666)
- 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
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- Alzheimer's disease, type 2 diabetes
- MeSH terms
- Actins, Aldehydes, Alzheimer Disease, Animals, Atrophy, Brain, Diabetes Mellitus, Type 2, Enzyme-Linked Immunosorbent Assay, Glial Fibrillary Acidic Protein, Insulin Resistance, Insulin-Like Growth Factor I, Mice, Inbred C57BL, Nerve Degeneration, Obesity, RNA, Messenger, Gene Expression, Amyloid beta-Peptides, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin, Adaptor Proteins, Signal Transducing, Mice, Insulin Receptor Substrate Proteins
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