Artigos de revisão
v. 2 n. 1 (2017): Revista Perspectiva: Ciência e Saúde
DOENÇA DE ALZHEIMER E DIABETES MELLITUS TIPO 2: Relações metabólicas e neurodegenerativas
- Leonardo Guimarães
- Camila Lazzaretti
-
Enviado
-
23 April 2024
-
Publicado
-
23-04-2024
Resumo
A Doença de Alzheimer (DA) é uma doença neurodegenerativa crônica, caracterizada pela perda progressiva da memória e da função cognitiva. Dentre os diferentes tipos de demência, a DA é a demência com maior prevalência no mundo.Caracteriza-se por alterações no sistema colinérgico e por desestruturação de células do hipocampo. Estas alterações são originadas pela hiperfosforilação da proteína TAU (intracelular) e presença de placas β-amilóides no encéfalo de pacientes com diagnóstico de DA. Recentemente, estudos vêm sugerindo que estes fatores possam ser desencadeados por alterações bioquímicas e fisiológicas características do Diabetes Mellitus tipo 2 (DM2), uma vez que ambos os transtornos possuem em sua grande maioria, níveis aumentados de glicose sanguínea. O presente trabalho teve por objetivo investigar a relação entre a glicemia aumentada levada pela DM2 com a DA. Para contemplar tal objetivo, foi realizada uma revisão narrativa de literatura nas bases de dados PubMed e SciELO. Consultou-se preferencialmente artigos empíricos, publicados nos últimos cinco anos, redigidos em inglês e em português. Estudos mostram que pacientes com DM2 possuem risco aumentado de desenvolver DA. Também se observa que a resistência à insulina e o nível elevado de glicose no organismo desencadeiam reações que estão de alguma forma associadas à hiperfosforilação da proteína TAU e ao depósito de placas β-amilóides em regiões encefálicas associadas à DA. Com os dados apontados na presente revisão, observou-se que na DA há uma complexidade de vias metabólicas e alterações encefálicas. Ainda assim, se destaca as complicações neuronais que podem resultar do manejo inapropriado do DM, como as mencionadas relações com a DA.
Referências
- World Health Organization.The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnosis guidelines. Geneva: World Health Organization; 1992.
- GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117—71
- Luo Z, Zhuang X, Kumar D, Wu X, Yue C, Han C, Lv J.The Correlation of Hippocampal T2-Mapping with Neuropsychology Test in Patients with Alzheimer’s Disease. PLoS ONE, 2013; 8(9), e76203. http://doi.org/10.1371/journal.pone.0076203
- Martinez A, Allodi S, Uziel D. Neuroanatomiaesssencial. Rio de Janeiro: Guanabara Koogan, 2015.
- Kandel ER, Schwartz JH, Jessel TM. Principles of neural science. New York: McGraw Hill; 2000.
- Grothe M, Heinsen H, Teipel S. Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer’s disease. NeurobiologyofAging, 2013;34(4), 1210–1220. http://doi.org/10.1016/j.neurobiolaging.2012.10.018
- Jia G, DeMarco VG, Sowers JR. Insulin resistance and hyperinsulina in diabetic cardiomyopathy. Nature Reviews. Endocrinology, 2016;12(3), 144–153. http://doi.org/10.1038/nrendo.2015.216
- Nelson DL, Cox MM. Princípios de bioquímica de Lehninger. Porto Alegre: Artmed, 2011. 6. ed. Porto Alegre: Artmed, 2014.
- International Diabetes Federation. IDF Diabetes Atlas, 6th edition. Brussels, Belgium: International Diabetes Federation; 2013. Available From: http://www.idf.org/diabetesatlas.
- Zhao Q, Zhou B, Ding D, Teramukai S, Guo Q, Fukushima M, Hong Z.Cognitive Decline in Patients with Alzheimer’s Disease and Its Related Factors in a Memory Clinic Setting, Shanghai, China. PLoS ONE, 2014; 9(4), e95755.http://doi.org/10.1371/journal.pone.0095755
- Baquero, M, Martín, N..Depressive symptoms in neurodegenerative diseases. World Journal of Clinical Cases : WJCC, 2015;3(8), 682–693. http://doi.org/10.12998/wjcc.v3.i8.682
- Rotomskis A, Margevičiūtė R, Germanavičius A, Kaubrys G, Budrys V, Bagdonas, A. Differential diagnosis of depression and Alzheimer’s disease with the Addenbrooke’s Cognitive Examination-Revised (ACE-R). BMC Neurology, 2015; 15, 57.http://doi.org/10.1186/s12883-015-0315-3
- Beato R, Amaral-Carvalho V, Guimarães H C, Tumas V, Souza CP, Oliveira GN de et al . Frontal assessment battery in a Brazilian sample of healthy controls: normative data. Arq. Neuro-Psiquiatr. [Internet]. 2012 Apr [cited 2016 Nov 09] ; 70( 4 ): 278-280. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2012000400011&lng=en. Epub Feb 24, 2012. http://dx.doi.org/10.1590/S0004-282X2012005000009.
- Harper L, Fumagalli GG., Barkhof F, Scheltens P, O’Brien JT, Bouwman F et al. MRI visual rating scales in the diagnosis of dementia: evaluation in 184 post-mortem confirmed cases. Brain, 2016;139(4), 1211–1225. http://doi.org/10.1093/brain/aww005
- Guimarães LC, Ferreira CF. Práticas de neuroimagem como promoção de diagnósticodiferencial entre Demência Frontotemporal e TranstornosNeuropsiquiátricos. VI Mostra Integrada de Iniciação Científica/ IV Seminário Integrado de Pós-Graduação; Jun 2015; Osório; Faculdade Cenecista de Osório – FACOS/CNEC: 2015.
- Kruse N, Schlossmacher MG, Schulz-Schaeffer WJ, Vanmechelen E, Vanderstichele H, El-Agnaf OM, Mollenhauer BA. First Tetraplex Assay for the Simultaneous Quantification of Total α-Synuclein, Tau, β-Amyloid42 and DJ-1 in Human Cerebrospinal Fluid. PLoS ONE, 2016; 11(4), e0153564. http://doi.org/10.1371/journal.pone.0153564
- Mun, Myung-Jin et al. Polymorphisms of small ubiquitin-related modifier genes are associated with risk of Alzheimer's disease in Korean: A case-control study.
- Journal of the Neurological Sciences ,2016; 364, 122 – 127http://dx.doi.org/10.1016/j.jns.2016.03.023
- Gui Y, Liu H, Zhang L, Lv W, Hu X. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease.Oncotarget, 2015;6(35), 37043–37053.
- van Bloemendaal L, Ijzerman RG, Ten Kulve JS, Barkhof F, Diamant M, Veltman DJ, van Duinkerken E. Alterations in white matter volume and integrity in obesity and type 2 diabetes.Metab Brain Dis. 2016 Jun;31(3):621-9. doi: 10.1007/s11011-016-9792-3.
- Barnea-Goraly N, Raman M, Mazaika P, Marzelli M, Hershey T, Weinzimer SA et al. For the Diabetes Research in Children Network (DirecNet): Alterations in White Matter Structure in Young Children With Type 1 Diabetes. Diabetes Care, 2014; 37(2),332–340.http://doi.org/10.2337/dc13-1388
- Antenor-Dorsey JAV, Meyer E, Rutlin J, Perantie DC., White, NH., Arbelaez AM, Hershey T et al. White Matter Microstructural Integrity in Youth With Type 1 Diabetes.Diabetes, 2013;62(2),581–589.http://doi.org/10.2337/db12-0696
- Umegaki H. Type 2 diabetes as a risk factor for cognitive impairment: current insights. Clinical Interventions in Aging, 2014; 9, 1011–1019.http://doi.org/10.2147/CIA.S48926
- Huang CC, Chung CM, Leu HB, Lin LY, Chiu CC, Hsu CY,Chan WL. Diabetes Mellitus and the Risk of Alzheimer’s Disease: A Nationwide Population-Based Study. PLoS ONE, 2014; 9(1), e87095. http://doi.org/10.1371/journal.pone.0087095
- Van Dijk G, van Heijningen S, Reijne AC, Nyakas C, van der Zee EA, Eisel ULM. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration.Frontiers in Neuroscience, 2015;9, 173.http://doi.org/10.3389/fnins.2015.00173
- Liu Z, Patil IY, Jiang T, Sancheti H, Walsh JP, Stiles BL et al. High-Fat Diet Induces Hepatic Insulin Resistance and Impairment of Synaptic Plasticity. PLoS ONE, 2015; 10(5), e0128274.http://doi.org/10.1371/journal.pone.0128274
- Jayaraman A, Lent-Schochet D, Pike CJ. Diet-induced obesity and low testosterone increase neuroinflammation and impair neural function. Journal of Neuroinflammation. 2014;11:162. doi:10.1186/s12974-014-0162-y.
- Lennertz RC, Medler KA, Bain JL, Wright DE, Stucky CL. Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy. Journal of Neurophysiology. 2011;106(2):905-914. doi:10.1152/jn.01123.2010.
- Mittal, K, Katare, DP. Shared links between type 2 diabetes mellitus and Alzheimer’s disease: A review. Diab Met Syndr: Clin Res Rev 2016; 10(2);144-149. http://dx.doi.org/10.1016/j.dsx.2016.01.021
- Bime C, Zhou T, Wang T, Slepian MJ, Garcia JGN, Hecker L. Reactive oxygen species–associated molecular signature predicts survival in patients with sepsis. Pulmonary Circulation, 2016;6(2), 196–201. http://doi.org/10.1086/685547
- Barbosa, KBF, Costa NMB, Alfenas RCG, De Paula SO, MINIM, VPR, Bressan J. Estresse oxidativo: conceito, implicações e fatores moduladores. Rev Nutr., Campinas, 2010;23(4): 629-643.
- Wu N, Shen H, Liu H, Wang Y, Bai Y, Han P. Acute blood glucose fluctuation enhances rat aorta endothelial cell apoptosis, oxidative stress and pro-inflammatory cytokine expression in vivo. Cardiovascular Diabetology. 2016;15:109. doi:10.1186/s12933-016-0427-0.
- Suresh S, Vijayakumar T. Correlations of Insulin Resistance and Serum Testosterone Levels with LH:FSH Ratio and Oxidative Stress in Women with Functional Ovarian Hyperandrogenism. Indian Journal of Clinical Biochemistry. 2015;30(3):345-350. doi:10.1007/s12291-014-0447-z.
- Lee S, Tong M, Hang S, Deochand C, de la Monte S. CSF and Brain Indices of Insulin Resistance, Oxidative Stress and Neuro-Inflammation in Early versus Late Alzheimer’s Disease. Journal of Alzheimer’s disease & Parkinsonism. 2013;3:128-. doi:10.4172/2161-0460.1000128.
- Verdile G, Keane KN, Cruzat VF, Medic S, Sabale M, Rowles J et al. Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer’s Disease. MediatorsofInflammation, 2015;105828. http://doi.org/10.1155/2015/105828
- Huang WJ, Zhang X, Chen WW. Role of oxidative stress in Alzheimer’s disease.BiomedicalReports, 2016;4(5), 519–522. http://doi.org/10.3892/br.2016.630
- Krumova P, Reyniers L, Meyer M, Lobbestael E, Stauffer D, Gerrits B, Muller L et al. Chemical genetic approach identifies microtubule affinity-regulating kinase 1 as a leucine-rich repeat kinase 2 substrate. FASEB J July 2015 29:2980-2992; published ahead of print April 8, 2015, doi:10.1096/fj.14-26232
- Chung PJ, Song C, Deek J, et al. Tau mediates microtubule bundle architectures mimicking fascicles of microtubules found in the axon initial segment. Nature Communications. 2016;7:12278. doi:10.1038/ncomms12278.
- Magi S, Castaldo P, Macrì ML, et al. Intracellular Calcium Dysregulation: Implications for Alzheimer’s Disease. BioMed Research International. 2016;2016:6701324. doi:10.1155/2016/6701324.
- Domise M, Didier S, Marinangeli C, et al. AMP-activated protein kinase modulates tau phosphorylation and tau pathology in vivo. Scientific Reports. 2016;6:26758. doi:10.1038/srep26758.
- Méphon-Gaspard A, Boca M, Pioche-Durieu C, et al. Role of tau in the spatial organization of axonal microtubules: keeping parallel microtubules evenly distributed despite macromolecular crowding. Cellular and Molecular Life Sciences. 2016;73(19):3745-3760. doi:10.1007/s00018-016-2216-z.
- Houck AL, Hernández F, Ávila J. A Simple Model to Study Tau Pathology. Journal of Experimental Neuroscience. 2016;10:31-38. doi:10.4137/JEN.S25100.
- Sydow A, Hochgräfe K, Könen S, et al. Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD. Acta Neuropathologica Communications. 2016;4:17. doi:10.1186/s40478-016-0281-z.
- Bukar Maina M, Al-Hilaly YK, Serpell LC. Nuclear Tau and Its Potential Role in Alzheimer’s Disease. Wischik CM, Harrington C, eds. Biomolecules. 2016;6(1):9. doi:10.3390/biom6010009.
- Šimić G, Babić Leko M, Wray S, et al. Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Bähler J, ed. Biomolecules. 2016;6(1):6. doi:10.3390/biom6010006.
- Hartmann Ana Paula Barbosa Jeronimo, Almeida Sérgio Monteiro de, Livramento José Antonio, Nitrini Ricardo, Takahashi Daniel, Caramelli Paulo. Hyperphosphorylated tau protein in the cerebrospinal fluid of patients with Alzheimer's disease and other dementias: preliminary findings. Arq. Neuro-psiquiatr. [Internet]. 2004 Sep [cited 2016 Nov 09] ; 62( 3b ): 751-755.. https://dx.doi.org/10.1590/S0004-282X2004000500001
- Ilievski V, Kinchen JM, Prabhu R, et al. Experimental Periodontitis Results in Prediabetes and Metabolic Alterations in Brain, Liver and Heart: Global Untargeted Metabolomic Analyses. Journal of oral biology (Northborough, Mass). 2016;3(1):10.13188/2377-987X.1000020.
- Kang Y, Cho M, Kim J, Kwon M, Peak J, Kang S, Yoon S, Song Y. Impaired macrophage autophagy induces systemic insulin resistance in obesity. Oncotarget, 2016; 7(24), 35577-35591.
- Morales-Corraliza J, Wong H, Mazzella MJ, et al. Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-β Alterations in a Monkey Model of Type 1 Diabetes. The Journal of Neuroscience. 2016;36(15):4248-4258. doi:10.1523/JNEUROSCI.4640-14.2016.
- Bhat V, Haeberlein B, Avila J. Glycogen synthase kinase 3: a drug target for CNS therapies. J. Neurochem 2004;89(6):1313-7
- Ono M, Watanabe H, Kitada A, Matsumura K, Ihara M, Saji H. Highly Selective Tau-SPECT Imaging Probes for Detection of Neurofibrillary Tangles in Alzheimer’s Disease. Scientific Reports. 2016;6:34197. doi:10.1038/srep34197.
- Bedse G, Di Domenico F, Serviddio G, Cassano T. Aberrant insulin signaling in Alzheimer’s disease: current knowledge. Frontiers in Neuroscience. 2015;9:204. doi:10.3389/fnins.2015.00204.
- Saharia K, Kumar R, Gupta K, Mishra S, Subramaniam JR. A Novel Way of Amelioration of Amyloid Beta Induced Toxicity in Caenorhabditis elegans. Annals of Neurosciences. 2016;23(3):149-154. doi:10.1159/000449180.
- Daschil N, Humpel C. Green-Fluorescent Protein+ Astrocytes Attach to Beta-Amyloid Plaques in an Alzheimer Mouse Model and Are Sensitive for Clasmatodendrosis. Frontiers in AgingNeuroscience,2016; 8, 75. http://doi.org/10.3389/fnagi.2016.00075