La enfermedad de Alzheimer y la diabetes mellitus
Resumen
Este trabajo hace una revisión de diferentes estudios que han reportado la relación de la diabetes mellitus (DM) con la Enfermedad de Alzheimer (EA) y viceversa. En la última década, se ha incrementado el número de trabajos centrados en encontrar nuevas evidencias que muestren la relación entre la DM y la EA. La DM y la EA comparten muchas características clínicas y bioquímicas: elevación del estrés oxidativo, inflamación, disfunción vascular, metabolismo de lípidos alterado, hipercolesterolemia, aumento de la formación de productos finales de glicación avanzada, patología mitocondrial y la alteración del metabolismo de la glucosa (sensibilidad a la insulina y el factor de crecimiento insulínico) que sugieren mecanismos patogénicos comunes. Recientemente se ha establecido que la inflamación del sistema nervioso central y periférico es la liga de la DM con la EA. Asimismo, se corroboró que la señalización defectuosa de insulina y la disfunción mitocondrial son características comunes en la EA y la DM. A pesar de los importantes hallazgos, se necesita la comprensión total de ambos procesos patológicos para determinar si estas enfermedades comparten las mismas dianas terapeúticas para tratamientos más efectivos e incluso detener el avance de la EA.
Abstract
This paper reviews various studies have reported the relationship of diabetes mellitus (DM) with Alzheimer's disease (AD). In the past decade has increased the number of studies on finding new evidence of the relationship between DM and AD. The DM and AD share many clinical and biochemical characteristics: elevation of oxidative stress, inflammation, vascular dysfunction, altered lipid metabolism, hypercholesterolemia, increased formation of advanced glycation end products, mitochondrial pathology and altered glucose metabolism (sensitivity to insulin and insulin-like growth factor) suggesting common pathogenic mechanisms. Recently it has been established that inflammation in the central nervous and peripheral system is the link between DM with EA. It was also confirmed that the defective insulin signaling and mitochondrial dysfunction are common features in AD and DM. Despite the important findings, full understanding of both disease processes are needed to determine whether these conditions share the same therapeutic targets for more effective treatments and even halt the progression of AD
Keywords: Alzheimer's disease; diabetes mellitus; insulin resistance; neuroinflammation; inflammation.
Palabras clave
Texto completo:
PDFReferencias
Herrera-Rivero M, Hernández-Aguilar M, Manzo J, Aranda-Abreu G. Enfermedad de Alzheimer: inmunidad y diagnóstico. Rev Neurol 2010 51: 153-164.
Weiping H, Cai L. Linking type 2 diabetes and Alzheimer’s disease. PNAS 2010 107: 6557-6558.
De Felice F, Lourenco M, Ferreira S. How does brain insulin resistance develop in Alzheimer's disease?. Alzheimers Dement 2014 10:S26-32
Alzheimer’s disease international. World Alzheimer report 2013, Journey of Caring, An analysis of long-term care for dementia. [Fecha de consulta: 01-08-2014] Disponibilidad: http://www.alz.co.uk/research/WorldAlzheimerReport2013ExecutiveSummary.pdf
International Diabetes Federation. IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, 2013. [Fecha de consulta: 12-08-2013] Disponibilidad: http://www.idf.org/diabetesatlas
Lue L, Andrade C, Sabbagh M, Walker D. Is there inflammatory synergy in type II diabetes mellitus and Alzheimer's disease?. J Alzheimers Dis 2012 1: 0-9.
Ferreira S, Clarke J, Bomfim T, De Felice F. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer’s disease. Alzheimers Dement 2014 10:S76-83.
Ott A, Stolk R, Hofman A, van Harskamp F, Grobbee D, Breteler M. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 1996 39: 1392-1397.
Ott A, Stolk R, van Harskamp F, Pols H, Hofman A, Breteler M. Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 1999 53: 1937-1942.
Schrijvers E, Witteman J, Sijbrands E, Hofman A, Koudstaal P, Breteler M. Insulin metabolism and the risk of Alzheimer´s disease: the Rotterdam Study. Neurology 2010 75: 1982-7.
Steen E, Terry B, Rivera E, Cannon J, Neely T, Tavares R, Xu X, Wands J, de la Monte S. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease - is this type 3 diabetes?. J Alzheimers Dis 2005 7: 63–80.
Kroner Z. The relationship between Alzheimer's disease and diabetes: type 3 diabetes?. Altern Med Rev 2009 14: 373-9.
Rivera E, Goldin A, Fulmer N, Tavares R, Wands J, de la Monte S. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J Alzheimers Dis 8: 247-268.
de la Monte S. Insulin resistance and Alzheimer's disease. BMB Rep 2009 42: 475-81.
Matsuzaki T, Sasaki K, Tanizaki Y, Hata J, Fujimi K, Matsui Y, Sekita A, Suzuki S, Kanba S, Kiyohara Y. Insulin resistance is associated with the pathology of Alzheimer´s disease: the Hisayama study. Neurology 2010 75: 764–770.
Cholerton B, Baker L, Craft S. Insulin resistance and pathological brain ageing. Diabetic Medicine 2011 28: 1463–1475.
de la Monte, S. Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer’s disease. Drugs 2012 72: 49–66.
Bosco D, Fava A, Plastino M, Montalcini T, Pujia, A. Possible implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis. J Cell Mol Med 2011 15: 1807– 1821.
Biessels G, Kappelle L. Increased risk of Alzheimer’s disease in type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? Biochem Soc Trans 2005 33: 1041-4.
de la Monte S. Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease. Curr Alzheimer Res 2012 9: 35-66.
Arab L, Sadeghi R, Walker D, Lue L, Sabbagh M. Consequences of Aberrant Insulin Regulation in the Brain: Can Treating Diabetes be Effective for Alzheimer's Disease. Neuropharmacol 2011 9: 693-705.
Min S, Joon H, Mook-Jung I. Insulin resistance and Alzheimer’s disease, topics in the prevention, treatment and complications of type 2 diabetes. En: Prof. Mark Zimering (Ed.). Topics in the Prevention, Treatment and Complications of Type 2 Diabetes. 2011. [Fecha de consulta: 12-01-2013] Disponible:
de la Monte S, Wands J. Alzheimer’s disease is type 3 diabetes - evidence reviewed. J Diabetes Sci Technol 2008 2: 1101-13.
Profenno L, Porsteinsson A, Faraone S. Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 2010 67: 505-12.
Adeghate E, Donáth T, Adem A. Alzheimer´s disease and diabetes mellitus: do they have anything in common?. Curr Alzheimer Res 2013 10: 609-617.
Pasquier F, Boulogne A, Leys D, Fontaine P. Diabetes mellitus and dementia. Diabetes Metab 2006 5: 403-414.
Hokama M, Oka S, Leon J, Ninomiya T, Honda H, Sasaki K, Iwaki T, Ohara T, Sasaki T, Frank M, LaFerla F, Kiyohara Y, Nakabeppu Y. Altered expression of diabetes-related genes in Alzheimer's disease brains: the Hisayama study. Cereb Cortex 2014 S24:2476-88.
van Himbergen T, Beiser A, Ai M. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer´s disease: results from the framingham heart study. Arch Neurol 2012 69: 594-600.
Fu W, Patel A, Jhamandas J. Amylin receptor: a common pathophysiological target in Alzheimer’s disease and diabetes mellitus. Front Aging Neurosci 2013 5:1-4.
Ke Y, Delerue F, Gladbach A, Götz J, Ittner L. Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer's disease. PLoS One 2009 4: e7917.
Abdul-Rahman O, Sasvari-Szekely M, Ver A, Rosta K, Szasz B, Kereszturi E, Keszler G. Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats. BMC Genomics 2012 13: 81.
Zhang Y, Zhou B, Deng B, Zhang F, Wu J, Wang Y, Le Y, Zhai Q. Amyloid-β induces hepatic insulin resistance in vivo via JAK2. Diabetes 2013 62:1159-66.
Currais A, Prior M, Lo D, Jolivalt C, Schubert D, Maher P. Diabetes exacerbates amyloid and neurovascular pathology in aging-accelerated mice. Aging Cell 2012 11: 1017-26.
Jolivalt C, Hurford R, Lee C, Dumaop W, Rockenstein E, Masliah E. Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice. Exp Neurol 2010 223: 422-31.
Aulston B, Odero G, Aboud Z, Glazner G. Alzheimer’s disease and diabetes. En: Prof. Inga Zerr (Ed.) Understanding Alzheimer’s Disease. 2013. [Fecha de consulta: 11-03-2013] Disponible: http://www.intechopen.com/books/understanding-alzheimer-s-disease/alzheimer-s-disease-and-diabetes.
Sims-Robinson C, Kim B, Rosko A, Feldman E. How does diabetes accelerate Alzheimer´s disease pathology?. Nat Rev Neurol 2010 6: 551-9.
De Felice F, Ferreira S. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer´s disease. Diabetes 2014 63: 2262-72.
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole G, Cooper N, Eikelenboom P, Emmerling M, Fiebich B, Finch C, Frautschy S, Griffin W, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie I, McGeer P, O'Banion M, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel F, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T. Inflammation and Alzheimer’s disease. Neurobiol Aging 2000 21: 383-421.
Walker D, Link J, Lue L, Dalsing-Hernandez J, Boyes B. Gene expression changes by amyloid beta peptide-stimulated human postmortem brain microglia identify activation of multiple inflammatory processes. J Leukoc Biol 2006 79: 596-610.
Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 2010 68: 930–41.
Klein W. Synaptotoxic amyloid-β oligomers: a molecular basis for the cause, diagnosis, and treatment of Alzheimer's disease?. J Alzheimers Dis 2013 33:S49-65
Morris J, Burns J. Insulin: an emerging treatment for Alzheimer's disease dementia?. Curr Neurol Neurosci 2012 12: 520-7.
Freiherr J, Hallschmid M, Frey W, Brünner Y, Chapman C, Hölscher C, Craft S, De Felice F, Benedict C. Intranasal insulin as a treatment for Alzheimer's disease: a review of basic research and clinical evidence. CNS Drugs 2013 27: 505-14.
Enlaces refback
- No hay ningún enlace refback.
eNeurobiología es una publicación cuatrimestral editada por el Instituto de Investigaciones Cerebrales de la Universidad Veracruzana. Estamos ubicados en Av. Dr. Luis Castelazo Ayala, s/n, colonia Industrial Ánimas, C.P. 91190, Xalapa-Enríquez, Veracruz, México. Teléfono: 8418900 ext. 13062, www.iice.uv.mx; eneurobiologia@uv.mx. Reserva de Derechos al Uso Exclusivo 04-2023-061314100600-102, otorgada por el Instituto Nacional de Derechos de Autor. ISSN: 2007-3054. Esta obra está bajo una Licencia Creative Commons Attribution 4.0 International.