medigraphic.com
SPANISH

Archivos de Neurociencias

Instituto Nacional de Neurología y Neurocirugía
  • Contents
  • View Archive
  • Information
    • General Information        
    • Directory
  • Publish
    • Instructions for authors        
  • medigraphic.com
    • Home
    • Journals index            
    • Register / Login
  • Mi perfil

2020, Number 4

<< Back Next >>

Arch Neurocien 2020; 25 (4)

Mechanisms of association between Alzheimer’s disease and diabetes mellitus: The insulin paradox

Hernández-Contreras KA, Martínez-Díaz JA, Hernández-Aguilar ME, Herrera-Covarrubias D, Rojas-Durán F, Aranda-Abreu GE
Full text How to cite this article

Language: Spanish
References: 60
Page: 45-54
PDF size: 638.99 Kb.


Key words:

Alzheimer’s, Diabetes, Insulin, Amyloid, Tau.

ABSTRACT

Between Alzheimer’s Disease (AD) and Diabetes Mellitus (DM) it has been evidenced that there are multiple mechanisms in common in both pathologies, ranging from cognitive deterioration in the clinical aspect to biochemical alterations of which the following can be highlighted; the increase in pro-inflammatory agents and excitotoxicity, increase in oxidative stress and increase in the final products of advanced glycation (AGEs), alterations in glucose metabolism, as well as alterations in the mTORC1 /S6 and GSK-3 pathways β; It also highlights the role of Insulin Resistance (Ri), where this alteration is linked to both AD and MD at various points in their physiopathology, either by influencing the different mechanisms mentioned above or directly. Objective. It is described how the influence of this hormone is such, whether its levels are high, effect known as hyperinsulinism or low effect known as hypoinsulinism, since both extremes lead to neurodegenerative effects characteristic of AD, mainly in the increase of β amyloid (Aβ) and hyperphosphorylated tau (pTau), through different processes. Contribution. We describe this phenomenon as “The insulin paradox”, in which the insulin/PI3K/Akt pathway also stands out as a crucial point, since independently of hyper or hypoinsulinism conditions this pathway is altered in both scenarios. This relationship between AD and DM is considered from the point of view of hypoglycemic treatments aimed at the attention of DM, which seem to interfere with AD, through several of the mechanisms in common that these pathologies have. Conclusion. Although it is too early to consider that these treatments for AD will give the same results in cases of AD, these data are valuable precedents in the search for therapeutic alternatives for AD.


REFERENCES

  1. Gale SA, Acar D, Daffner KR. Dementia. Am J Med. 2018;131(10):1161- 1169. https://www.ncbi.nlm.nih.gov/pubmed/29425707

  2. Patterson C. Alzheimer’s Disease International. The World Alzheimer Report. 20184-7. https://www.alzint.org/resource/world-alzheimer-report-2018/

  3. Spittau B. Aging Microglia-Phenotypes, Functions and Implications for Age-Related Neurodegenerative Diseases. Front Aging Neurosci. 2017;9:194. https://www.ncbi.nlm.nih.gov/pubmed/28659790

  4. McDade E, Bateman RJ. Stop Alzheimer’s before it starts. Nature.2017; 547(7662):153-155. https://www.ncbi.nlm.nih.gov/pubmed/28703214

  5. Neumiller JJ et al. Professional Practice Committee: Standards of Medical Care in Diabetes-2019. 2019 https://doi.org/10.2337/dc19-SppC01

  6. Harreiter J, Roden M. [Diabetes mellitus-Definition, classification, diagnosis, screening and prevention (Update 2019)]. Wien Klin Wochenschr. 2019; 131(S1):6-15. doi: 10.1007/s00508-019-1450-4

  7. Petersmann A, et al. Definition, Classification and Diagnosis of Diabetes Mellitus. Exp Clin Endocrinol Diabetes. 2018;126(7):406-410. https:// www.ncbi.nlm.nih.gov/pubmed/29975979

  8. Cisternas P., Inestrosa N.C. Brain glucose metabolism: Role of Wnt signaling in the metabolic impairment in Alzheimer’s disease. Neurosci Biobehav Rev. 2017; 80:316-328. https://www.ncbi.nlm.nih.gov/ pubmed/28624434

  9. Dodd G.T., Tiganis T. Insulin action in the brain: Roles in energy and glucose homeostasis. J Neuroendocrinol. 2017; 29(10). https://www. ncbi.nlm.nih.gov/pubmed/28758251

  10. Mestizo-Gutiérrez S.L., Hernández-Aguilar M.E., Rojas-Durán F., Manzo- Denes J., Abreu G.E.A. La enfermedad de Alzheimer y la Diabetes Mellitus. Rev. eNeurobiol. 2014; 1-14. https://www.uv.mx/eneurobiologia/ vols/2014/10/Mestizo/HTML.html

  11. Bloom G.S., Lazo J.S., Norambuena A. Reduced brain insulin signaling: a seminal process in Alzheimer’s disease pathogenesis. Neuropharmacol. 2018;136(Pt B):192-195. https://www.ncbi.nlm.nih. gov/pubmed/28965829

  12. Li J., Cesari M., Liu F., Dong B, Vellas B. Effects of Diabetes Mellitus on cognitive decline in patients with Alzheimer Disease: A Systematic Review. Can J Diabetes. 2017; 41(1):114-119. https://www.ncbi.nlm.nih.gov/ pubmed/27614804

  13. Stanley M., Macauley S.L., Holtzman D.M. Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence. J Exp Med. 2016; 213(8):1375-1385. https://www.ncbi.nlm.nih.gov/pubmed/27432942

  14. Rajmohan R., Reddy P.H. Amyloid-Beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. J Alzheimers Dis. 2017; 57(4):975-999. https://www.ncbi.nlm. nih.gov/pubmed/27567878

  15. Zuroff L., Daley D., Black K.L., Koronyo-Hamaoui M. Clearance of cerebral Aß in Alzheimer’s disease: reassessing the role of microglia and monocytes. Cell Mol Life Sci. 2017; 74(12):2167-2201. https://www. ncbi.nlm.nih.gov/pubmed/28197669

  16. Carroll C.M., Li Y.M. Physiological and pathological roles of the α-secretase complex. Brain Res Bull. 2016;126(Pt 2):199-206. https:// www.ncbi.nlm.nih.gov/pubmed/27133790

  17. Pascoal T.A., et al. Amyloid-ß and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer’s disease. Mol Psychiatry. 2017;22(2):306-311. https://www.ncbi.nlm.nih.gov/ pubmed/27021814

  18. Medeiros R., Baglietto-Vargas D., LaFerla F.M. The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther. 2011;17(5):514-524 https://www.ncbi.nlm.nih.gov/pubmed/20553310

  19. Guo T., Dakkak D., Rodriguez-Martin T., Noble W., Hanger DP. A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response. Acta Neuropathol Commun. 2019; 7(1):2.https://www.ncbi.nlm.nih.gov/pubmed/30606258

  20. Eisenberg D.S., Sawaya M.R. Neurodegeneration: Taming tangled tau. Nature. 2017; 547(7662):170-171. https://www.ncbi.nlm.nih.gov/ pubmed/28678777

  21. Alzheimer’s A. 2016 Alzheimer’s disease facts and figures. Alzheimers Dement. 2016; 12(4):459-509. https://www.ncbi.nlm.nih.gov/pubmed/27570871

  22. Mosconi L. Glucose metabolism in normal aging and Alzheimer’s disease: methodological and physiological considerations for PET studies. Clin Transl Imaging. 2013;1(4) https://www.ncbi.nlm.nih.gov/pubmed/24409422

  23. Andersen J.V., Christensen S.K., Aldana B.I., Nissen J.D., Tanila H., Waagepetersen H.S. Alterations in cerebral cortical glucose and glutamine metabolism precedes amyloid plaques in the APPswe/PSEN1dE9 mouse model of Alzheimer’s disease. Neurochem Res. 2017;42(6):1589-1598. https://www.ncbi.nlm.nih.gov/pubmed/27686658

  24. Pourfarzam M., Zadhoush F., Sadeghi M. The difference in correlation between insulin resistance index and chronic inflammation in type 2 diabetes with and without metabolic syndrome. Adv Biomed Res. 2016; 5:153.https://www.ncbi.nlm.nih.gov/pubmed/27713874

  25. Cuéllar A.Y.D., Sibaja C.M., Aguirre A.U. Endocrinología clínica de Dorantes y Martínez. Editorial El manual Moderno; 2016. https://books. google.com/s&lr=&id=9bEjDAAAQBAJ&oi=fnd&pg=PT46&dq=Endoc rinología+clínica+de+Dorantes+y+Martínez.+5a.+ed.+México,+D. F&ots=BbNVBWJDY_&sig=4HRCEwS0_AWWF4sgVXWEf0YOaDQ

  26. Kanat M., DeFronzo R.A.., Abdul-Ghani M.A. Treatment of prediabetes. World J Diabetes. 2015;6(12):1207-1222. https://www.ncbi.nlm.nih. gov/pubmed/26464759

  27. Roden M. Diabetes mellitus–definition, klassifikation und diagnose. Wiener klinische Wochenschrift. 2016;128(2):37-40. https://link. springer.com/article/10.1007/s00508-015-0931-3

  28. Vieira M.N.N., Lima-Filho R.A.S., De Felice F.G. Connecting Alzheimer’s disease to diabetes: underlying mechanisms and potential therapeutic targets. Neuropharmacol. 2018; 136(Pt B):160-171.https://www.ncbi. nlm.nih.gov/pubmed/29129775

  29. Simó R., Ciudin A., Simó-Servat O., Hernández C. Cognitive impairment and dementia: a new emerging complication of type 2 diabetes-The diabetologist’s perspective. Acta Diabetol. 2017;54(5):417-424. https:// www.ncbi.nlm.nih.gov/pubmed/28210868

  30. Wu J., et al. High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: a potential molecular mechanism for diabetesinduced cognitive dysfunction. Oncotarget. 2017; 8(25):40843-40856. https://www.ncbi.nlm.nih.gov/pubmed/28489581

  31. Li Z.G., Zhang W., Sima A.A. Alzheimer-like changes in rat models of spontaneous diabetes. Diabetes. 2007; 56(7):1817-1824. https://www. ncbi.nlm.nih.gov/pubmed/17456849

  32. Sajan M., et al. Brain insulin signaling is increased in insulin-resistant states and decreases in FOXOs and PGC-1α and increases in Aß1-40/42 and phospho-tau may Abet Alzheimer Development. Diabetes. 2016;65(7):1892-1903. https://www.ncbi.nlm.nih.gov/ pubmed/26895791

  33. Steen E., et al. 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(1):63-80. https://www.ncbi.nlm.nih.gov/ pubmed/15750215

  34. Liu J., Chang L., Song Y., Li H., Wu Y. The Role of NMDA Receptors in Alzheimer’s Disease. Front Neurosci. 2019; 13:43. https://www.ncbi. nlm.nih.gov/pubmed/3080005

  35. van Bussel F.C., et al. Increased GABA concentrations in type 2 diabetes mellitus are related to lower cognitive functioning. Medicine (Baltimore). 2016;95(36): e4803. https://www.ncbi.nlm.nih.gov/pubmed/27603392

  36. Petersen M.C., Shulman G.I. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-2223. https://www.ncbi.nlm. nih.gov/pubmed/30067154

  37. Baglietto-Vargas D., Shi J., Yaeger D.M., Ager R., LaFerla F.M. Diabetes and Alzheimer’s disease crosstalk. Neurosci Biobehav Rev. 2016; 64:272-287. https://www.ncbi.nlm.nih.gov/pubmed/26969101

  38. Paouri E., Tzara O., Kartalou G.I., Zenelak S., Georgopoulos S. Peripheral tumor necrosis factor-alpha (TNF-α) modulates amyloid pathology by regulating blood-derived immune cells and glial response in the brain of AD/TNF transgenic mice. J Neurosci. 2017;37(20):5155-5171. https:// www.ncbi.nlm.nih.gov/pubmed/28442538

  39. Butterfield D.A., Boyd-Kimball D. Oxidative stress, amyloid-ß peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer’s Disease. J Alzheimers Dis. 2018;62(3):1345-1367. https:// www.ncbi.nlm.nih.gov/pubmed/29562527

  40. Cheignon C., Tomas M., Bonnefont-Rousselot D., Faller P., Hureau C, Collin F. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol. 2018; 14:450-464. https://www.ncbi.nlm.nih.gov/ pubmed/29080524

  41. Cai Z., et al. Role of RAGE in Alzheimer’s Disease. Cell Mol Neurobiol. 2016;36(4):483-495. https://www.ncbi.nlm.nih.gov/ pubmed/26175217

  42. González-Reyes R.E., Aliev G., Ávila-Rodrigues M., Barreto G.E. Alterations in glucose metabolism on cognition: a possible link between diabetes and dementia. Curr Pharm Des. 2016;22(7):812-818. https:// www.ncbi.nlm.nih.gov/pubmed/26648470

  43. Altschul D.M., Starr J.M., Deary I.J. Cognitive function in early and later life is associated with blood glucose in older individuals: analysis of the Lothian Birth Cohort of 1936. Diabetologia. 2018;61(9):1946-1955. https://www.ncbi.nlm.nih.gov/pubmed/29860628

  44. Kim B., Backus C., Oh S., Hayes J.M., Feldman E.L. Increased tau phosphorylation and cleavage in mouse models of type 1 and type 2 diabetes. Endocrinology. 2009;150(12):5294-5301. https://www.ncbi. nlm.nih.gov/pubmed/19819959

  45. Ke Y.D., Delerue F., Gladbach A., Götz J., Ittner L.M. Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer’s disease. PLoS One. 2009;4(11): e7917. https://www.ncbi. nlm.nih.gov/pubmed/19936237

  46. An Y., et al. Evidence for brain glucose dysregulation in Alzheimer’s disease. Alzheimers Dement. 2018;14(3):318-329. https://www.ncbi. nlm.nih.gov/pubmed/29055815

  47. Lester-Coll N., Rivera E.J., Soscia S.J., Doiron K., Wands J.R., de la Monte S.M. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. J Alzheimers Dis. 2006;9(1):13-33 https:// www.ncbi.nlm.nih.gov/pubmed/16627931

  48. Sinagoga K.L., et al. Distinct roles for the mTOR pathway in postnatal morphogenesis, maturation and function of pancreatic islets. Development. 2017; 144(13):2402-2414. https://www.ncbi.nlm.nih.gov/ pubmed/28576773

  49. Kickstein E., et al. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci U S A. 2010; 107(50):21830-21835. https://www.ncbi.nlm.nih.gov/ pubmed/21098287

  50. Zhang Y., et al. Diabetes mellitus and Alzheimer’s disease: GSK-3ß as a potential link. Behav Brain Res. 2018; 339:57-65. https://www.ncbi.nlm. nih.gov/pubmed/29158110

  51. Qu Z.S., et al. Glycogen synthase kinase-3 regulates production of amyloid-ß peptides and tau phosphorylation in diabetic rat brain. The Scientific World Journal. 2014;2014 http://downloads.hindawi.com/ journals/tswj/2014/878123.pdf

  52. Amin J., et al. Effect of amyloid-ß(Aß) immunization on hyperphosphorylated tau: a potential role for glycogen synthase kinase (GSK)-3ß. Neuropathol Appl Neurobiol. 2015; 41(4):445-457. https://www.ncbi.nlm.nih.gov/ pubmed/25486988

  53. Tam J.H., Seah C., Pasternak S.H. The amyloid precursor protein is rapidly transported from the golgi apparatus to the lysosome and where it is processed into beta-amyloid. Mol Brain. 2014;7:54. https://www.ncbi. nlm.nih.gov/pubmed/25085554

  54. Freude S, et al. Peripheral hyperinsulinemia promotes tau phosphorylation in vivo. Diabetes. 2005; 54(12):3343-3348.

  55. Freude S., et al. Neuronal IGF-1 resistance reduces Abeta accumulation and protects against premature death in a model of Alzheimer’s disease. FASEB J. 2009; 23(10):3315-3324. https://www.ncbi.nlm.nih.gov/ pubmed/19487308

  56. Devi L., Alldred M.J., Ginsberg S.D., Ohno M. Mechanisms underlying insulin deficiency-induced acceleration of ß-amyloidosis in a mouse model of Alzheimer’s disease. PloS one. 2012;7(3): e32792. https:// journals.plos.org/plosone/article?id=10.1371/journal.pone.0032792

  57. Kalra S. Diabesity. J Pak Med Assoc. 2013;63(4):532-534. https://www. ncbi.nlm.nih.gov/pubmed/23905459

  58. 58.de la Monte SM, Tong M, Lester-Coll N, Plater M, Wands JR. Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. J Alzheimers Dis. 2006;10(1):89-109. https://www.ncbi.nlm.nih.gov/pubmed/16988486

  59. Takeda S., et al. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci U S A. 2010;107(15):7036- 7041.https://www.ncbi.nlm.nih.gov/pubmed/20231468

  60. Valente T., Gella A., Fernández-Busquets X., Unzeta M., Durany N. Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer’s disease and diabetes mellitus. Neurobiol Dis. 2010; 37(1):67-76. https://www.ncbi.nlm.nih.gov/pubmed/19778613




2020     |     www.medigraphic.com

Mi perfil

C?MO CITAR (Vancouver)

Arch Neurocien. 2020;25