Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links
At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseas...
- Autores:
-
Rojas, Milagros
Chávez-Castillo, Mervin
Ba, Jordan
Ortega, Ángel
Nava, Manuel
Salazar, Juan
Díaz-Camargo, Edgar
Rojas-Quintero, Joselyn
Bermúdez, Valmore
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Simón Bolívar
- Repositorio:
- Repositorio Digital USB
- Idioma:
- eng
- OAI Identifier:
- oai:bonga.unisimon.edu.co:20.500.12442/8410
- Acceso en línea:
- https://hdl.handle.net/20.500.12442/8410
http://dx.doi.org/10.4239/wjd.v12.i6.745
https://www.wjgnet.com/1948-9358/full/v12/i6/745.htm
- Palabra clave:
- Alzheimer’s disease
Type 2 diabetes mellitus
Oxidative stress
Islet amyloid polypeptide
Glucagon-like peptide 1
Cognitive dysfunction
Hypoglycemic agents
- Rights
- openAccess
- License
- Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| spellingShingle |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links Alzheimer’s disease Type 2 diabetes mellitus Oxidative stress Islet amyloid polypeptide Glucagon-like peptide 1 Cognitive dysfunction Hypoglycemic agents |
| title_short |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_full |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_fullStr |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_full_unstemmed |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| title_sort |
Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links |
| dc.creator.fl_str_mv |
Rojas, Milagros Chávez-Castillo, Mervin Ba, Jordan Ortega, Ángel Nava, Manuel Salazar, Juan Díaz-Camargo, Edgar Rojas-Quintero, Joselyn Bermúdez, Valmore |
| dc.contributor.author.none.fl_str_mv |
Rojas, Milagros Chávez-Castillo, Mervin Ba, Jordan Ortega, Ángel Nava, Manuel Salazar, Juan Díaz-Camargo, Edgar Rojas-Quintero, Joselyn Bermúdez, Valmore |
| dc.subject.eng.fl_str_mv |
Alzheimer’s disease Type 2 diabetes mellitus Oxidative stress Islet amyloid polypeptide Glucagon-like peptide 1 Cognitive dysfunction Hypoglycemic agents |
| topic |
Alzheimer’s disease Type 2 diabetes mellitus Oxidative stress Islet amyloid polypeptide Glucagon-like peptide 1 Cognitive dysfunction Hypoglycemic agents |
| description |
At present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD. |
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2021 |
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2021-09-17T16:49:56Z |
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2021-09-17T16:49:56Z |
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2021 |
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Artículo científico |
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Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-766 |
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19489358 |
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https://hdl.handle.net/20.500.12442/8410 |
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http://dx.doi.org/10.4239/wjd.v12.i6.745 |
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https://www.wjgnet.com/1948-9358/full/v12/i6/745.htm |
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Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-766 19489358 |
| url |
https://hdl.handle.net/20.500.12442/8410 http://dx.doi.org/10.4239/wjd.v12.i6.745 https://www.wjgnet.com/1948-9358/full/v12/i6/745.htm |
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eng |
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eng |
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Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
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pdf |
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Baishideng Publishing Group Inc |
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World Journal of Diabetes |
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Rojas, Milagrosd07a9d4d-cce2-438c-b4a0-fc5ed4af1a67Chávez-Castillo, Mervin912e1d3d-18fb-43af-8edb-826137f74a5aBa, Jordan03e0da9a-c765-4242-99cc-c9599355d347Ortega, Ángelb6a809bb-4d26-4e53-9419-e4eb9fb40a9bNava, Manuelcf0ca570-5fc3-4ec7-9913-90be952261e2Salazar, Juanfbd053e7-5aea-424c-812f-92153ecb9181Díaz-Camargo, Edgare056554f-7c70-4102-b9c6-bad4ba6afb39Rojas-Quintero, Joselyn1fcd6ac1-186e-465c-a5fd-3c25563275abBermúdez, Valmore29f9aa18-16a4-4fd3-8ce5-ed94a0b8663a2021-09-17T16:49:56Z2021-09-17T16:49:56Z2021Rojas M, Chávez-Castillo M, Bautista J, Ortega Á, Nava M, Salazar J, Díaz-Camargo E, Medina O, Rojas-Quintero J, Bermúdez V. Alzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links. World J Diabetes 2021; 12(6): 745-76619489358https://hdl.handle.net/20.500.12442/8410http://dx.doi.org/10.4239/wjd.v12.i6.745https://www.wjgnet.com/1948-9358/full/v12/i6/745.htmAt present, Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.pdfengBaishideng Publishing Group IncAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2World Journal of DiabetesVol. 12, No.6 (2021)Alzheimer’s diseaseType 2 diabetes mellitusOxidative stressIslet amyloid polypeptideGlucagon-like peptide 1Cognitive dysfunctionHypoglycemic agentsAlzheimer’s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics linksinfo:eu-repo/semantics/articleArtículo científicohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1World Health Organization. Dementia. [cited 21 October 2020]. In: World Health Organization [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/dementiaAmerican Diabetes Association. 12. Older Adults: Standards of Medical Care in Diabetes-2020. Diabetes Care 2020; 43: S152-S162 [PMID: 31862755 DOI: 10.2337/dc20-S012]International Diabetes Federation. Worldwide toll of diabetes. [cited 21 October 2020]. In: International Diabetes Federation [Internet]. Available from: https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.htmInternational Diabetes Federation. Worldwide toll of diabetes. [cited 21 October 2020]. In: International Diabetes Federation [Internet]. Available from: https://diabetesatlas.org/en/sections/worldwide-toll-of-diabetes.htmAlicic RZ, Rooney MT, Tuttle KR. Diabetic Kidney Disease: Challenges, Progress, and Possibilities. Clin J Am Soc Nephrol 2017; 12: 2032-2045 [PMID: 28522654 DOI: 10.2215/CJN.11491116]Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012; 35: 556-564 [PMID: 22301125 DOI: 10.2337/dc11-1909]Mirhoseini M, Saleh N, Momeni A, Deris F, Asadi-Samani M. A study on the association of diabetic dermopathy with nephropathy and retinopathy in patients with type 2 diabetes mellitus. J Nephropathol 2016; 5: 139-143 [PMID: 27921026 DOI: 10.15171/jnp.2016.26]Thiruvoipati T, Kielhorn CE, Armstrong EJ. Peripheral artery disease in patients with diabetes: Epidemiology, mechanisms, and outcomes. World J Diabetes 2015; 6: 961-969 [PMID: 26185603 DOI: 10.4239/wjd.v6.i7.961]Xue M, Xu W, Ou YN, Cao XP, Tan MS, Tan L, Yu JT. Diabetes mellitus and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 144 prospective studies. Ageing Res Rev 2019; 55: 100944 [PMID: 31430566 DOI: 10.1016/j.arr.2019.100944]Dá Mesquita S, Ferreira AC, Sousa JC, Correia-Neves M, Sousa N, Marques F. Insights on the pathophysiology of Alzheimer's disease: The crosstalk between amyloid pathology, neuroinflammation and the peripheral immune system. Neurosci Biobehav Rev 2016; 68: 547-562 [PMID: 27328788 DOI: 10.1016/j.neubiorev.2016.06.014]Sandhir R, Gupta S. Molecular and biochemical trajectories from diabetes to Alzheimer's disease: A critical appraisal. World J Diabetes 2015; 6: 1223-1242 [PMID: 26464760 DOI: 10.4239/wjd.v6.i12.1223]Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest 2016; 126: 12-22 [PMID: 26727229 DOI: 10.1172/JCI77812]Craft S, Claxton A, Baker LD, Hanson AJ, Cholerton B, Trittschuh EH, Dahl D, Caulder E, Neth B, Montine TJ, Jung Y, Maldjian J, Whitlow C, Friedman S. Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer's Disease Biomarkers: A Pilot Clinical Trial. J Alzheimers Dis 2017; 57: 1325-1334 [PMID: 28372335 DOI: 10.3233/JAD-161256]Koepsell H. Glucose transporters in brain in health and disease. Pflugers Arch 2020; 472: 1299-1343 [PMID: 32789766 DOI: 10.1007/s00424-020-02441-xMergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain: the role of glucose in physiological and pathological brain function. Trends Neurosci 2013; 36: 587-597 [PMID: 23968694 DOI: 10.1016/j.tins.2013.07.001]McAllister MS, Krizanac-Bengez L, Macchia F, Naftalin RJ, Pedley KC, Mayberg MR, Marroni M, Leaman S, Stanness KA, Janigro D. Mechanisms of glucose transport at the blood-brain barrier: an in vitro study. Brain Res 2001; 904: 20-30 [PMID: 11516408 DOI: 10.1016/s0006-8993(01)02418-0]Jurcovicova J. Glucose transport in brain - effect of inflammation. Endocr Regul 2014; 48: 35-48 [PMID: 24524374 DOI: 10.4149/endo_2014_01_35]Qutub AA, Hunt CA. Glucose transport to the brain: a systems model. Brain Res Brain Res Rev 2005; 49: 595-617 [PMID: 16269321 DOI: 10.1016/j.brainresrev.2005.03.002]Bedse G, Di Domenico F, Serviddio G, Cassano T. Aberrant insulin signaling in Alzheimer's disease: current knowledge. Front Neurosci 2015; 9: 204 [PMID: 26136647 DOI: 10.3389/fnins.2015.00204]Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer's disease. Front Endocrinol (Lausanne) 2014; 5: 161 [PMID: 25346723 DOI: 10.3389/fendo.2014.00161]Rojas J, Bermúdez V, Leal E, Cano R, Luti Y, Acosta L, Finol F, AparicioD, Arraiz N, Linares S, Rojas E, Canelón R, Deisiree S. Insulinorresistencia e hiperinsulinemia como factores de riesgo para enfermedad cardiovascular. Arch Venez Farmacol Ter 2008; 27: 30-40Baranowska-Bik A, Bik W. Insulin and brain aging. Prz Menopauzalny 2017; 16: 44-46 [PMID: 28721128 DOI: 10.5114/pm.2017.68590]Tascone LDS, Bottino CMC. Neurobiology of neuropsychiatric symptoms in Alzheimer's disease: A critical review with a focus on neuroimaging. Dement Neuropsychol 2013; 7: 236-243 [PMID: 29213845 DOI: 10.1590/S1980-57642013DN70300002]Narvaez E, Pelaez J, Almeida K, Alvarez C, Mendoza C, Morales A, Godos D, Del Salto Ocaña T, Catota M. Implication of apolipoprotein e polymorphisms in the atherosclerosis and Alzheimer’s disease physiopathology. Rev Latinoam Hipertens 2018; 13: 97-102Gilbert BJ. 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Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules 2016; 6: 6 [PMID: 26751493 DOI: 10.3390/biom6010006]Tsartsalis S, Xekardaki A, Hof PR, Kövari E, Bouras C. Early Alzheimer-type lesions in cognitively normal subjects. Neurobiol Aging 2018; 62: 34-44 [PMID: 29107845 DOI: 10.1016/j.neurobiolaging.2017.10.002]Sonne DP, Hemmingsen B. Comment on American Diabetes Association. Standards of Medical Care in Diabetes-2017. Diabetes Care 2017;40(Suppl. 1):S1-S135. Diabetes Care 2017; 40: e92-e93 [PMID: 28637892 DOI: 10.2337/dc17-0299]Jayaraman A, Pike CJ. Alzheimer's disease and type 2 diabetes: multiple mechanisms contribute to interactions. Curr Diab Rep 2014; 14: 476 [PMID: 24526623 DOI: 10.1007/s11892-014-0476-2]Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis 2015; 44: 897- 906 [PMID: 25374101 DOI: 10.3233/JAD-141791]Frölich L, Blum-Degen D, Bernstein HG, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Türk A, Hoyer S, Zöchling R, Boissl KW, Jellinger K, Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm (Vienna) 1998; 105: 423-438 [PMID: 9720972 DOI: 10.1007/s007020050068]Craft S, Peskind E, Schwartz MW, Schellenberg GD, Raskind M, Porte D Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 1998; 50: 164-168 [PMID: 9443474 DOI: 10.1212/wnl.50.1.164]Craft S, Asthana S, Schellenberg G, Baker L, Cherrier M, Boyt AA, Martins RN, Raskind M, Peskind E, Plymate S. Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype. Ann N Y Acad Sci 2000; 903: 222-228 [PMID: 10818510 DOI: 10.1111/j.1749-6632.2000.tb06371.x]Craft S, Asthana S, Cook DG, Baker LD, Cherrier M, Purganan K, Wait C, Petrova A, Latendresse S, Watson GS, Newcomer JW, Schellenberg GD, Krohn AJ. Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype. Psychoneuroendocrinology 2003; 28: 809-822 [PMID: 12812866 DOI: 10.1016/s0306-4530(02)00087-2]Baker LD, Cross DJ, Minoshima S, Belongia D, Watson GS, Craft S. Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes. 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