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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Insulin resistance, a hallmark of diabetes, develops in Alzheimer's brains.
“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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“The chronic HFD fed mice developed obesity and T2DM associated with fasting hyperglycemia, hyper-lipidemia, and increased serum pro-inflammatory cytokine levels as previously reported [63,64].”
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“Furthermore, as 70% of diabetic patients also have hypercholesterolemia, the DMHC pig model provides a unique opportunity to study the effects of DM and HC, the two most common co-morbidities [12, 35, 52, 59].”
The Liver-Brain Axis of Alcohol-Mediated Neurodegeneration: Role of Toxic Lipids
de la Monte, S. M., Longato, L., Tong, M., DeNucci, S. M., & Wands, J. R. (2009) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph6072055 · Cited by 137 · see citing works
“Steatohepatitis was associated with liver and brain insulin resistance manifested by reduced insulin receptor (IR) binding, IR gene expression, IR tyrosine kinase activation, and insulin responsive gene expression, including those required for metabolism or neurotransmitter synthesis [104-110], and increased oxidative…”
BackgroundLongato, L., Ripp, K., Setshedi, M., Dostálek, M., Akhlaghi, F., Branda, M., Wands, J. R., & de la Monte, S. M. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/479348 · Cited by 133 · see citing works
“1% Triton X-100, and protease and phosphatase inhibitors [38].”
BackgroundInsulin dysfunction and Tau pathology
Khoury, N. B. E., Gratuze, M., Papon, M.-A., Bretteville, A., & Planel, E. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00022 · Cited by 131 · see citing works
“Moreover, Moroz et al. have demonstrated that HFD-induced T2DM leads to an increase in mRNA levels of IRS-1 and IRS4 in the brain of non-transgenic mice (Moroz et al., 2008).”
BackgroundInfluentialShefer, G., Marcus, Y., & Stern, N. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.07.015 · Cited by 124 · see citing works
Longato, L., Tong, M., Wands, J. R., & de la Monte, S. M. (2011) · Hepatology Research · doi:10.1111/j.1872-034x.2011.00934.x · Cited by 117 · see citing works
Bhat, N. R., & Thirumangalakudi, L. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121030 · Cited by 116 · see citing works
“[52] found limited AD-type changes including tau phosphorylation with no IIS impairment in C57BL/6 mice fed a high fat diet.”
Backgroundde la Monte, S. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111727 · Cited by 101 · see citing works
“At the same time, postmortem human brain studies demonstrated no significant increase in AD diagnosis among diabetics [206], and in experimental models and humans with obesity, T2DM, or other peripheral insulin resistance diseases, the severity of neurodegeneration and brain insulin resistance tend to be relatively mi…”
Leboucher, A., Laurent, C., Fernández-Gómez, F.-J., Burnouf, S., Troquier, L., Eddarkaoui, S., Demeyer, D., Caillierez, R., Zommer, N., Vallez, E., et al. (2012) · Diabetes · doi:10.2337/db12-0866 · Cited by 96 · see citing works
Asadbegi, M., Yaghmaei, P., Salehi, I., Ebrahim‐Habibi, A., & Komaki, A. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.02.005 · Cited by 87 · see citing works
Intranasal insulin therapy for cognitive impairment and neurodegeneration: current state of the art
de la Monte, S. M. (2013) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2013.856877 · Cited by 87 · see citing works
“In the brain, insulin has critical roles in regulating neuronal functions such as growth, metabolism, plasticity, survival and cholinergic function, which are needed for learning and memory [9,17-19].”
de la Monte, S. M., Tong, M., Lawton, M., & Longato, L. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-54 · Cited by 87 · see citing works
Mechanisms of Ceramide-Mediated Neurodegeneration
Tong, M., & de la Monte, S. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0983 · Cited by 84 · see citing works
“Altogether, the neurodegenerative effects of C6 ceramide treatment resembled many of the abnormalities caused by chronic HFD feeding, in that both resulted in increased insulin and IRS-4 expression, decreased ChAT and GAPDH expression, and increased 4-HNE and ubiquitin immunoreactivity [53].”
InfluentialGhrelin: a link between ageing, metabolism and neurodegenerative disorders.
Stoyanova, I. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.026 · Cited by 80 · see citing works
“Obesity and diabetes mellitus (DM) are associated with increased risk of developing dementia and AD (Moroz et al., 2008).”
Backgroundde la Monte, S. M., Re, E. B., Longato, L., & Tong, M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111728 · Cited by 80 · see citing works
“Tissues were homogenized in lysis buffer supplemented with protease and phosphatase inhibitors [31].”
MethodThe neuroenergetics of stress hormones in the hippocampus and implications for memory
Osborne, D. M., Pearson-Leary, J., & McNay, E. C. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00164 · Cited by 78 · see citing works
“Decreased brain glucose supply during hypoglycemia impairs memory (Korol and Gold, 1998; Messier, 2004), and conditions that impair brain glucose metabolism (such as type 2 diabetes, or Alzheimer’s disease) also cause cognitive impairment (Moroz et al., 2008; de la Monte, 2012).”
BackgroundNeurodegeneration in type 2 diabetes: Alzheimer's as a case study
Madhusudhanan, J., Suresh, G., & Devanathan, V. (2020) · Brain and Behavior · doi:10.1002/brb3.1577 · Cited by 76 · see citing works
de la Monte, S. M., Tong, M., & Wands, J. R. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170829 · Cited by 75 · see citing works
“The approach was to evaluate the integrity of brain insulin and IGF signaling networks in mouse [49, 50] and rat [51, 52] models of obesity produced by chronic high fat diet feeding.”
Relationships Between Diabetes and Cognitive Impairment
de la Monte, S. M. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.09.006 · Cited by 71 · see citing works
“Epidemiologic and longitudinal studies demonstrated increased risks for MCI or AD in people with glucose intolerance, T2DM, obesity/dyslipidemic disorders, or deficits in insulin secretion.105–107 More recently, investigators linked increased rates of cognitive impairment to chronic hyperglycemia,108 which precedes th…”
InfluentialQuintessential Risk Factors: Their Role in Promoting Cognitive Dysfunction and Alzheimer’s Disease
Daulatzai, M. A. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0854-6 · Cited by 72 · see citing works
“In a C57BL/6 mouse model of obesity and DM, high fat diet (HFD) feeding (for 16 weeks) doubled body weight and caused DM [393].”
BackgroundTong, M., Longato, L., & de la Monte, S. M. (2010) · BMC Endocrine Disorders · doi:10.1186/1472-6823-10-4 · Cited by 70 · see citing works
DeNucci, S. M., Tong, M., Longato, L., Lawton, M., Setshedi, M., Carlson, R. I., Wands, J. R., & de la Monte, S. M. (2010) · Gastroenterology Research and Practice · doi:10.1155/2010/312790 · Cited by 68 · see citing works
“Competitive equilibrium binding studies were used to measure effects of chronic ethanol feeding on insulin, IGF-1, and IGF-2 receptor binding [20, 31].”
MethodMoy, G. A., & McNay, E. C. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.11.008 · Cited by 66 · see citing works
“Of note, caffeine has also been shown to offer protection against neurodegenerative conditions such as Alzheimer’s disease (AD), for which T2DM is a major risk factor [7, 31, 36-43], as well as e.”
BackgroundObesity and brain illness: from cognitive and psychological evidences to obesity paradox
Monda, V., Marra, M. L., Perrella, R., Caviglia, G., Iavarone, A., Chieffi, S., Messina, G., Carotenuto, M., Monda, M., & Messina, A. (2017) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s148392 · Cited by 63 · see citing works
“Plasma amyloid proteins have been found in obesity, 40,41 and it is suggestive of increased risk of AD.”
BackgroundInfluentialFrom obesity to Alzheimer's disease through insulin resistance
Terzo, S., Amato, A., & Mulè, F. (2021) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2021.108026 · Cited by 62 · see citing works
de la Monte, S. M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-3540-2_4 · Cited by 59 · see citing works
de la Monte, S. M. (2012) · PubMed · Cited by 58 · see citing works
Cytokines: How important are they in mediating sickness?
Poon, D. C.-H., Ho, J. Y. S., Chiu, K., & Chang, R. C. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.11.001 · Cited by 57 · see citing works
“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.”
Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease
de la Monte, S. M. (2012) · Frontiers in Bioscience-Elite · doi:10.2741/e482 · Cited by 56 · see citing works
Heydarpour, F., Sajadimajd, S., Mirzarazi, E., Haratipour, P., Joshi, T., Farzaei, M. H., Khan, H., & Echeverría, J. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.498758 · Cited by 55 · see citing works
“Neuronal dysfunction and cognitive impairment in dementia have also been shown to have a strong association with b cell failure, such that AD is known as the type 3 diabetes in literature (Ott et al., 1996; Steen et al., 2005; Moroz et al., 2008; Chen and Zhong, 2013).”
BackgroundThe link between iron, metabolic syndrome, and Alzheimer’s disease
Grünblatt, E., Bartl, J., & Riederer, P. F. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0426-3 · Cited by 56 · see citing works
“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).”
MethodResultAutophagy-lysosome dysfunction is involved in Aβ deposition in STZ-induced diabetic rats
Ma, L., Lv, Y.-L., Huo, K., Liu, J., Shang, S., Fei, Y., Li, Y., Zhao, B., Wei, M., Deng, Y., et al. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.10.031 · Cited by 55 · see citing works
Morys, F., Initiative, A. D. N., Potvin, O., Zeighami, Y., Vogel, J. W., Lamontagne‐Caron, R., Duchesne, S., & Dagher, A. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220535 · Cited by 54 · see citing works
Kong, S. H., Park, Y. J., Lee, J., Cho, N. H., & Moon, M. K. (2018) · Scientific Reports · doi:10.1038/s41598-017-18998-0 · Cited by 52 · see citing works
Acharya, N. K., Qi, X., Goldwaser, E. L., Godsey, G. A., Wu, H., Kosciuk, M. C., Freeman, T. A., Macphee, C. H., Wilensky, R. L., Venkataraman, V., et al. (2017) · Diabetes and Vascular Disease Research · doi:10.1177/1479164116683149 · Cited by 51 · see citing works
Therapeutic targets of brain insulin resistance in sporadic Alzheimer's disease
Suzanne, M. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/482 · Cited by 50 · see citing works
Chou, S., Ajoy, R., Changou, C. A., Hsieh, Y.-T., Wang, Y.-K., & Hoffer, B. J. (2016) · Scientific Reports · doi:10.1038/srep37659 · Cited by 49 · see citing works
“We thus studied the de-phosphorylation of IRS-1S302 ex vivo under (1) saline for 5 min as control; (2) insulin (10 nM), 5 min; (3) CCL5 (10 ng/ml), 5 min; (4) insulin and CCL5 together for 5 min, or (5) 10 min pretreatment with an antagonist Met-CCL5 (MCCL5, 10 ng/ml) followed by insulin stimulation for another 5 min.”
MethodMa, Y., Wu, D., & LIU, J.-K. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2012.1186 · Cited by 48 · see citing works
Setshedi, M., Longato, L., Petersen, D. R., Ronis, M. J. J., Chen, W. C., Wands, J. R., & de la Monte, S. M. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01569.x · Cited by 48 · see citing works
“Relative mRNA abundance was calculated from the ng ratios of specific mRNA to 18S measured in the same samples (Moroz et al., 2008).”
MethodPan, Y., Li, J., Lin, P., Wan, L., Qu, Y., Cao, L., & Wang, L. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1348410 · Cited by 49 · see citing works
Anderson, N. J., King, M. R., Delbruck, L., & Jolivalt, C. G. (2014) · Disease Models & Mechanisms · doi:10.1242/dmm.015750 · Cited by 43 · see citing works
“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.”
BackgroundGlucagon-like peptide-2 reduces the obesity-associated inflammation in the brain
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 · see citing works
Evidence for Cortical Neuronal Loss in Male Type 2 Diabetic Goto-Kakizaki Rats
Hussain, S., Mansouri, S., Sjöholm, Å., Patrone, C., & Darsalia, V. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131958 · Cited by 41 · see citing works
“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 · see citing works
“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.”
Koga, S., Kojima, A., Kuwabara, S., & Yoshiyama, Y. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.04.028 · Cited by 40 · see citing works
Ghrelin-Attenuated Cognitive Dysfunction in Streptozotocin-induced Diabetic Rats
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 · see citing works
Role of insulin resistance in Alzheimer’s disease
Cai, Z., Xiao, M., Chang, L., & Yan, L. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9631-3 · Cited by 38 · see citing works
“Thus, the impairment of insulin signaling pathway by IR could link tau pathology and Aβ (Moroz et al. 2008).”
BackgroundTo, 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 · see citing works
“However, other studies report no such changes [44,47].”
BackgroundResultIron metabolism in diabetes-induced Alzheimer’s disease: a focus on insulin resistance in the brain
Chung, J. Y., Kim, H.-S., & Song, J. (2018) · BioMetals · doi:10.1007/s10534-018-0134-2 · Cited by 37 · see citing works
Golubnitschaja, O. (2010) · The EPMA Journal · doi:10.1007/s13167-010-0014-5 · Cited by 36 · see citing works
Balasubramanian, P., Kiss, T., Gulej, R., Toth, A. N., Tarantini, S., Yabluchanskiy, A., Ungvari, Z. I., & Csiszár, A. (2024) · Nutrients · doi:10.3390/nu16070952 · Cited by 33 · see citing works
Kacířová, M., Železná, B., Blažková, M., et al. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02190-3 · Cited by 32 · see citing works
Is Elevated Norepinephrine an Etiological Factor in Some Cases of Alzheimers Disease?
Fitzgerald, P. J. (2010) · Current Alzheimer Research · doi:10.2174/156720510792231775 · Cited by 32 · see citing works
“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].”
BackgroundPeng, 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 28 · see citing works
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 28 · see citing works
Environmental Exposure, Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms
Aitlhadj, L., Ávila, D. S., Benedetto, A., Aschner, M., & Stürzenbaum, S. R. (2010) · Environmental Health Perspectives · doi:10.1289/ehp.1002522 · Cited by 27 · see citing works
de la Monte, S. M. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-230555 · Cited by 27 · see citing works
“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].”
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 · see citing works
Liou, C. J., Tong, M., Vonsattel, J. P., & de la Monte, S. M. (2019) · ASN NEURO · doi:10.1177/1759091419839515 · Cited by 26 · see citing works
“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).”
MethodInfluentialn-3 PUFA and obesity: from peripheral tissues to the central nervous system
de Mello, A. H., Uberti, M. F., de Farias, B. X., de Souza, N. A. R., & Rezin, G. T. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114518000429 · Cited by 25 · see citing works
“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.”
McNay, E. C., & Recknagel, A. K. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.11.001 · Cited by 25 · see citing works
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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 · see citing works
The relationships between obesity and epilepsy: A systematic review with meta-analysis
Li, Y.-X., Guo, W., Chen, R.-X., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0306175 · Cited by 23 · see citing works
“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].”
Neurodegeneration in juvenile Iberian pigs with diet-induced nonalcoholic fatty liver disease
Zeltser, N., Meyer, I., Hernandez, G. V., Trahan, M. J., Fanter, R. K., Abo-Ismail, M. K., Glanz, H., Strand, C. R., Burrin, D. G., Frano, M. R. L., et al. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00120.2020 · Cited by 23 · see citing works
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The metabolic and neuroinflammatory changes induced by consuming a cafeteria diet are age-dependent
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 · see citing works
Diabesity and Brain Energy Metabolism: The Case of Alzheimer’s Disease
Cardoso, S., Seiça, R. M. F., & Moreira, P. I. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-63260-5_5 · Cited by 22 · see citing works
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“, 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.”
BackgroundRanolazine Attenuates Brain Inflammation in a Rat Model of Type 2 Diabetes
Cassano, V., Tallarico, M., Armentaro, G., Sarro, C. D., Iannone, M., Leo, A., Russo, E., Citraro, R., Sarro, G. D., Hribal, M. L., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416160 · Cited by 19 · see citing works
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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 · see citing works
“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
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Does obesity put your brain at risk?
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Changes of myelin basic protein in the hippocampus of an animal model of type 2 diabetes
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Preclinical models of disease and multimorbidity with focus upon cardiovascular disease and dementia
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Protein Modification by Dicarbonyl Molecular Species in Neurodegenerative Diseases
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“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].”
BackgroundNeuropathology of type 2 diabetes: a short review on insulin-related mechanisms
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- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Epidemiology › 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
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.
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