Cited by 151Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAdipokines, Inflammation, and Metabolic Diseases

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Limited Alzheimer-Type Neurodegeneration in Experimental Obesity and Type 2 Diabetes Mellitus

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Moroz, Natalie, Tong, Ming, Longato, Lisa, Xu, Haiyan, de la Monte, Suzanne M.·2008·Journal of Alzheimer s Disease

DOI 10.3233/jad-2008-15103PMC PMC10074393

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Abstract

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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Background
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Background
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Background
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BackgroundInfluential
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Background
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Background
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Method
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Background
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Background
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Method
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Background
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BackgroundInfluential
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“There is evidence to show that obesity (Moroz et al., 2008; Yi et al., 2012), diabetes (Luo et al., 2002; Moroz et al., 2008), and alcohol abuse (Zhao et al., 2013) can cause activation of microglia and astrocytes.”
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Background
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“In an obesity/T2DM mouse model, using high fat diet, Moroz et al. demonstrated a link between AD and T2DM showing that both present insulin resistance in the brain, but still where not fully similar to the neuropathology in AD (Moroz et al. 2008).”
MethodResult
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Method
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“Relative mRNA abundance was calculated from the ng ratios of specific mRNA to 18S measured in the same samples (Moroz et al., 2008).”
Method
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Role of insulin impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice
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“C57 mice fed a HFD have increased TG levels but no detectable alteration of level or distribution of APP, Aβ, phosphorylated tau (Moroz et al., 2008) or synaptophysin in the brain and no water maze deficits after 5 and 10 months on HFD (Mielke et al.”
Background
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Nuzzo, D., Baldassano, S., Amato, A., Picone, P., Galizzi, G., Caldara, G., Carlo, M. D., & Mulè, F. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.10.012 · Cited by 43
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Hussain, S., Mansouri, S., Sjöholm, Å., Patrone, C., & Darsalia, V. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131958 · Cited by 42
“Rodent studies provide evidence that T2D itself cognitive decline and dementia [15] and Moroz et al have observed the development of AD-like symptoms in T2D mice, where the brain mass was marginally [16].”
The Beneficial Role of Vitamin D in Alzheimer’s Disease
Lương, K. V. Q., & Nguyễn, L. (2011) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317511429321 · Cited by 40
“In a C57BL/6 mouse model of obesity and type 2 DM, high-fat diet feeding for 16 weeks doubled mean body weight, caused type 2 DM, marginally reduced mean brain weight, and was associated with significantly increased levels of tau, 89 suggesting that obesity and type 2 DM may contribute to AD.”
Immunohistochemical analysis of tau phosphorylation and astroglial activation with enhanced leptin receptor expression in diet-induced obesity mouse hippocampus
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Ma, L., Zhang, D., Tang, Y. C., Lu, Y., Zhang⋆, Y., Gao, Y., Li, X., Zhao, K., Chai, L., & Xiao, Q. (2011) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31820ce536 · Cited by 40
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Cai, Z., Xiao, M., Chang, L., & Yan, L. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9631-3 · Cited by 38
“Thus, the impairment of insulin signaling pathway by IR could link tau pathology and Aβ (Moroz et al. 2008).”
Background
The ε3 and ε4 Alleles of Human APOE Differentially Affect Tau Phosphorylation in Hyperinsulinemic and Pioglitazone Treated Mice
To, A. W. M., Ribé, E. M., Chuang, T. T., Schroeder, J. E., & Lovestone, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016991 · Cited by 37
“However, other studies report no such changes [44,47].”
BackgroundResult
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Time for new guidelines in advanced diabetes care: Paradigm change from delayed interventional approach to predictive, preventive & personalized medicine
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Aging and high-fat diet feeding lead to peripheral insulin resistance and sex-dependent changes in brain of mouse model of tau pathology THY-Tau22
Kacířová, M., Železná, B., Blažková, M., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02190-3 · Cited by 32
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Fitzgerald, P. J. (2010) · Current Alzheimer Research · doi:10.2174/156720510792231775 · Cited by 34
“However, mice fed a high fat diet to induce obesity and type 2 diabetes mellitus, did not exhibit AD histopathology, increases in amyloid-beta or phospho-tau, or impairrments in insulin-like growth factor signaling or acetylcholine homeostasis [103].”
Background
High-Fat-Diet-Induced Weight Gain Ameliorates Bone Loss without Exacerbating AβPP Processing and Cognition in Female APP/PS1 Mice
Peng, Y., Liu, J., Tang, Y., Liu, J., Han, T., Han, S., Li, H., Hou, C., Liu, J., & Long, J. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00225 · Cited by 30
Diabesity and brain disturbances: A metabolic perspective
Cardoso, S., & Moreira, P. I. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.10.002 · Cited by 31
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Aitlhadj, L., Ávila, D. S., Benedetto, A., Aschner, M., & Stürzenbaum, S. R. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.1002522 · Cited by 28
Malignant Brain Aging: The Formidable Link Between Dysregulated Signaling Through Mechanistic Target of Rapamycin Pathways and Alzheimer’s Disease (Type 3 Diabetes)
de la Monte, S. M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230555 · Cited by 28
“Chronic high fat feeding, in addition to obesity, causes cognitive impairment, brain atrophy, increased tau phosphorylation, oxidative stress, neu-roinﬂammation [116, 117, 187, 188], and deﬁcits in cholinergic function [189].”
Diabetes negatively affects cortical and striatal GABAergic neurons: an effect that is partially counteracted by exendin-4
Larsson, M., Lietzau, G., Nathanson, D., Östenson, C., Mallard, C. E., Johansson, M. E., Nyström, T., Patrone, C., & Darsalia, V. (2016) · Bioscience Reports · doi:10.1042/bsr20160437 · Cited by 27
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“Frontal (Brodmann’s areas [BA]8/9 and BA24) and tem- poral (BA38) lobe cortical tissue homogenates were prepared in 5 volumes of lysis buffer containing 50 mM Tris (pH 7.5), 150 mM NaCl, 5 mM EDTA (pH 8.0), 50 mM NaF, 0.1% Triton X-100, and protease and phosphatase inhibitors (Moroz et al., 2008).”
MethodInfluential
n-3 PUFA and obesity: from peripheral tissues to the central nervous system
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“In rodent studies, Moroz et al.((81)) showed that high-fat-diet feeding increased lipid peroxidation in the hippocampus, as indicated by high 4-hydroxynonenal levels.”
Reprint of: ‘Brain insulin signaling: A key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes’
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Marra, M. L., Ilardi, C. R., Villano, I., Carosella, M., Staiano, M., Iavarone, A., Chieffi, S., Messina, G., Polito, R., Scarinci, A., et al. (2022) · Brain Sciences · doi:10.3390/brainsci12081080 · Cited by 30
Prolonged diet induced obesity has minimal effects towards brain pathology in mouse model of cerebral amyloid angiopathy: Implications for studying obesity–brain interactions in mice
Zhang, L., Dasuri, K., Fernandez-Kim, S.-O., Bruce‐Keller, A. J., Freeman, L. R., Pepping, J. K., Beckett, T. L., Murphy, M. P., & Keller, J. N. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.01.002 · Cited by 24
Chronic peripheral hyperinsulinemia has no substantial influence on tau phosphorylation in vivo
Becker, K., Freude, S., Zemva, J., Stöhr, O., Krone, W., & Schubert, M. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.04.022 · Cited by 24
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“Obesity elevates oxidative stress through nicotinamide adenine dinucleotide phosphate oxidase, augments prostaglandin E2 levels, and activates the B-cell nuclear factor-κ B light chain enhancer [67, 68].”
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Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health
Marttila, S., Rovio, S., Mishra, P. P., Seppälä, I., Lyytikäinen, L., Juonala, M., Waldenberger, M., Oksala, N., Ala‐Korpela, M., Harville, E. W., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-88465-4 · Cited by 23
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Teixeira, D., Cecconello, A. L., Partata, W. A., de Fraga, L. S., Ribeiro, M. F. M., & Guedes, R. P. (2017) · Nutritional Neuroscience · doi:10.1080/1028415x.2017.1380892 · Cited by 25
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Cardoso, S., Seiça, R. M. F., & Moreira, P. I. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-63260-5_5 · Cited by 24
Elevation of cortical C26:0 due to the decline of peroxisomal β-oxidation potentiates amyloid β generation and spatial memory deficits via oxidative stress in diabetic rats
Shi, Y., Sun, X.-C., Sun, Y., Hou, L., Yao, M., Lian, K., Li, J., Lu, X., & Jiang, L. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.11.067 · Cited by 21
“, 2004) and animal (Moroz et al., 2008; Guglielmotto et al., 2010; De Felice and Ferreira, 2014) studies, an association of DM and neurodegenerative disorders, as well as memory decline, has been described.”
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Understanding the mechanisms of disease modifying effects of aerobic exercise in people with Alzheimer’s disease
Abdullahi, A., Wong, T. W. L., & Ng, S. S. M. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102202 · Cited by 21
Heat shock response and insulin-associated neurodegeneration
Urban, M. J., Dobrowsky, R. T., & Blagg, B. S. J. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.11.001 · Cited by 19
“Tau hyperphosphorylation in wild-type diabetic mice is comparatively less than diabetic pR5 mice, suggesting that insulin depletion enhances, but does not initiate, tauopathy [89].”
Oxidative stress: from molecular studies to clinical intervention strategies
Gao, Q., Jiang, L., Sun, Y., An, X., Sun, W., Tang, S., Kang, X., Zhao, X., Li, Z., Liu, C., et al. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1638042 · Cited by 19
A Direct Relationship Between ‘Blood Stasis’ and Fibrinaloid Microclots in Chronic, Inflammatory, and Vascular Diseases, and Some Traditional Natural Products Approaches to Treatment
Kell, D. B., Pretorius, E., & Zhao, H. (2025) · Pharmaceuticals · doi:10.3390/ph18050712 · Cited by 17
Does obesity put your brain at risk?
Al-Dalaeen, A. M., & Al-Domi, H. A. (2022) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2022.102444 · Cited by 17
Alzheimer’s Disease, Obesity, and Type 2 Diabetes: Focus on Common Neuroglial Dysfunctions (Critical Review and New Data on Human Brain and Models)
Tolédano, A., Rodríguez‐Casado, A., Álvarez, M., & Toledano‐Díaz, A. (2024) · Brain Sciences · doi:10.3390/brainsci14111101 · Cited by 19
Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes
Nam, S. M., Kwon, H. J., Kim, W., Kim, J. W., Hahn, K. R., Jung, H. Y., Kim, D. W., Yoo, D. Y., Seong, J. K., Hwang, I. K., et al. (2018) · Laboratory Animal Research · doi:10.5625/lar.2018.34.4.176 · Cited by 17
Preclinical models of disease and multimorbidity with focus upon cardiovascular disease and dementia
Shabir, O., Moll, T., Matuszyk, M. M., Eyre, B., Dake, M. D., Berwick, J., & Francis, S. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111361 · Cited by 17
Protein Modification by Dicarbonyl Molecular Species in Neurodegenerative Diseases
Williams, W. M., Weinberg, A., & Smith, M. A. (2011) · Journal of Amino Acids · doi:10.4061/2011/461216 · Cited by 16
“Although both diseases exhibit some similarities, such as insulin resistance [64], dysregulation of iron homeostasis, and increases in metallothionein and heme oxygenase-1 [65], there is limited evidence that Type 1 or Type 2 diabetes leads to AD neuropathology [66].”
Background
Neuropathology of type 2 diabetes: a short review on insulin-related mechanisms
Guerrero‐Berroa, E., Schmeidler, J., & Beeri, M. S. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.019 · Cited by 14

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
ORCID: Moroz, Natalie
Tong, Ming
Xu, Haiyan
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
DOI: 10.3233/jad-2008-15103
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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Limited Alzheimer-Type Neurodegeneration in Experimental Obesity and Type 2 Diabetes Mellitus

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