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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

Ⅱ型糖尿病患者血浆BACE1水平和BACE1 C786G基因多态性与认知功能的关系:横断面研究

卷 17, 期 4, 2020

页: [355 - 364] 页: 10

弟呕挨: 10.2174/1567205017666200522210957

价格: $65

摘要

背景:在Ⅱ型糖尿病(T2DM)和轻度认知障碍(MCI)的病理生理过程中，β-位点APP裂解酶1 (BACE1)是一个关键酶。我们的目的是研究Ⅱ型糖尿病MCI患者血浆BACE1水平和BACE1基因多态性与不同认知表现的潜在关联。 方法:根据蒙特利尔认知评估(MoCA)评分，将186例Ⅱ型糖尿病患者分为92例MCI组和94例健康认知对照组。对社会人口统计学特征、临床参数和神经心理学测试进行了评估。测定BACE1 C786G基因多态性及血浆BACE1水平。 结果:MCI患者血浆BACE1水平高于对照组。MCI组在调整空腹血糖、糖化血红蛋白和c肽稳态模型评估胰岛素抵抗后，血浆BACE1水平与MoCA、时钟绘制测验和逻辑记忆测验成绩呈负相关，与Trail Making Test- b时间呈正相关(均p<0.05)。多变量logistic回归分析显示，Ⅱ型糖尿病患者血浆BACE1水平高，MCI风险显著增加(OR = 1.492, p = 0.027)。T2DM-MCI患者血浆GG和GC基因型BACE1水平明显高于CC基因型(p = 0.035);p = 0.026)。 结论:血浆BACE1水平升高与T2DM-MCI患者整体认知功能低下，尤其是视空间能力、视/逻辑记忆和执行功能低下相关。此外，血浆BACE1水平升高是T2DM患者MCI的危险因素，可能与BACE1 C786G基因突变有关。

关键词: β-位点APP裂解酶1

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[1]
Stranahan AM. Models and mechanisms for hippocampal dysfunction in obesity and diabetes. Neuroscience 2015; 309: 125-39.
[http://dx.doi.org/10.1016/j.neuroscience.2015.04.045] [PMID: 25934036]
[2]
Bhutada P, Mundhada Y, Humane V, et al. Agmatine, an endogenous ligand of imidazoline receptor protects against memory impairment and biochemical alterations in streptozotocin-induced diabetic rats. Prog Neuropsychopharmacol Biol Psychiatry 2012; 37(1): 96-105.
[http://dx.doi.org/10.1016/j.pnpbp.2012.01.009] [PMID: 22300747]
[3]
Mariani E, Monastero R, Mecocci P. Mild cognitive impairment: A systematic review. J Alzheimers Dis 2007; 12(1): 23-35.
[http://dx.doi.org/10.3233/JAD-2007-12104] [PMID: 17851192]
[4]
Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 2006; 5(1): 64-74.
[http://dx.doi.org/10.1016/S1474-4422(05)70284-2] [PMID: 16361024]
[5]
Janson J, Laedtke T, Parisi JE, O’Brien P, Petersen RC, Butler PC. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes 2004; 53(2): 474-81.
[http://dx.doi.org/10.2337/diabetes.53.2.474] [PMID: 14747300]
[6]
Strachan MW, Reynolds RM, Marioni RE, Price JF. Cognitive function, dementia and type 2 diabetes mellitus in the elderly. Nat Rev Endocrinol 2011; 7(2): 108-14.
[http://dx.doi.org/10.1038/nrendo.2010.228] [PMID: 21263438]
[7]
Gaspar JM, Baptista FI, Macedo MP, Ambrósio AF. Inside the diabetic brain: Role of different players involved in cognitive decline. ACS Chem Neurosci 2016; 7(2): 131-42.
[http://dx.doi.org/10.1021/acschemneuro.5b00240] [PMID: 26667832]
[8]
Laird FM, Cai H, Savonenko AV, et al. BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions. J Neurosci 2005; 25(50): 11693-709.
[http://dx.doi.org/10.1523/JNEUROSCI.2766-05.2005] [PMID: 16354928]
[9]
McConlogue L, Buttini M, Anderson JP, et al. Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP Transgenic Mice. J Biol Chem 2007; 282(36): 26326-34.
[http://dx.doi.org/10.1074/jbc.M611687200] [PMID: 17616527]
[10]
Cai H, Wang Y, McCarthy D, et al. BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat Neurosci 2001; 4(3): 233-4.
[http://dx.doi.org/10.1038/85064] [PMID: 11224536]
[11]
Vassar R, Bennett BD, Babu-Khan S, et al. Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999; 286(5440): 735-41.
[http://dx.doi.org/10.1126/science.286.5440.735] [PMID: 10531052]
[12]
Yan R, Bienkowski MJ, Shuck ME, et al. Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity. Nature 1999; 402(6761): 533-7.
[http://dx.doi.org/10.1038/990107] [PMID: 10591213]
[13]
Lesné SE, Sherman MA, Grant M, et al. Brain amyloid-β oligomers in ageing and Alzheimer’s disease. Brain 2013; 136(Pt 5): 1383-98.
[http://dx.doi.org/10.1093/brain/awt062] [PMID: 23576130]
[14]
Holsinger RM, McLean CA, Beyreuther K, Masters CL, Evin G. Increased expression of the amyloid precursor beta-secretase in Alzheimer’s disease. Ann Neurol 2002; 51(6): 783-6.
[http://dx.doi.org/10.1002/ana.10208] [PMID: 12112088]
[15]
Fukumoto H, Cheung BS, Hyman BT, Irizarry MC. Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 2002; 59(9): 1381-9.
[http://dx.doi.org/10.1001/archneur.59.9.1381] [PMID: 12223024]
[16]
Vassar R. BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease. Alzheimers Res Ther 2014; 6(9): 89.
[http://dx.doi.org/10.1186/s13195-014-0089-7] [PMID: 25621019]
[17]
Gold G, Blouin JL, Herrmann FR, et al. Specific BACE1 genotypes provide additional risk for late-onset Alzheimer disease in APOE epsilon 4 carriers. Am J Med Genet 2003; 119B(1): 44-7.
[18]
Yu M, Liu Y, Shen J, Lv D, Zhang J. Meta-analysis of BACE1 gene rs638405 polymorphism and the risk of Alzheimer’s disease in Caucasion and Asian population. Neurosci Lett 2016; 616: 189-96.
[http://dx.doi.org/10.1016/j.neulet.2016.01.059] [PMID: 26828303]
[19]
Kan R, Wang B, Zhang C, et al. Genetic association of BACE1 gene polymorphism C786G with late-onset Alzheimer’s disease in Chinese. J Mol Neurosci 2005; 25(2): 127-31.
[20]
Kirschling CM, Kölsch H, Frahnert C, Rao ML, Maier W, Heun R. Polymorphism in the BACE gene influences the risk for Alzheimer’s disease. Neuroreport 2003; 14(9): 1243-6.
[http://dx.doi.org/10.1097/00001756-200307010-00011] [PMID: 12824768]
[21]
Clarimón J, Bertranpetit J, Calafell F, Boada M, Tàrraga L, Comas D. Association study between Alzheimer’s disease and genes involved in Abeta biosynthesis, aggregation and degradation: Suggestive results with BACE1. J Neurol 2003; 250(8): 956-61.
[http://dx.doi.org/10.1007/s00415-003-1127-8] [PMID: 12928915]
[22]
Nowotny P, Kwon JM, Chakraverty S, Nowotny V, Morris JC, Goate AM. Association studies using novel polymorphisms in BACE1 and BACE2. Neuroreport 2001; 12(9): 1799-802.
[http://dx.doi.org/10.1097/00001756-200107030-00008] [PMID: 11435901]
[23]
Cruts M, Dermaut B, Rademakers R, et al. Amyloid beta secretase gene (BACE) is neither mutated in nor associated with early-onset Alzheimer’s disease. Neurosci Lett 2001; 313(1-2): 105-7.
[http://dx.doi.org/10.1016/S0304-3940(01)02234-0] [PMID: 11684351]
[24]
Todd S, McKnight AJ, Liu WW, et al. BACE1 polymorphisms do not influence platelet membrane beta-secretase activity or genetic susceptibility for Alzheimer’s disease in the Northern Irish population. Neuromolecular Med 2008; 10(4): 368-76.
[http://dx.doi.org/10.1007/s12017-008-8045-y] [PMID: 18581272]
[25]
Huse JT, Byant D, Yang Y, et al. Endoproteolysis of beta-secretase (beta-site amyloid precursor protein-cleaving enzyme) within its catalytic domain. A potential mechanism for regulation. J Biol Chem 2003; 278(19): 17141-9.
[http://dx.doi.org/10.1074/jbc.M213303200] [PMID: 12551920]
[26]
Meakin PJ, Harper AJ, Hamilton DL, et al. Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. Biochem J 2012; 441(1): 285-96.
[http://dx.doi.org/10.1042/BJ20110512] [PMID: 21880018]
[27]
Plucińska K, Dekeryte R, Koss D, et al. Neuronal human BACE1 knockin induces systemic diabetes in mice. Diabetologia 2016; 59(7): 1513-23.
[http://dx.doi.org/10.1007/s00125-016-3960-1] [PMID: 27138913]
[28]
Lee HJ, Ryu JM, Jung YH, et al. High glucose upregulates BACE1-mediated Aβ production through ROS-dependent HIF-1α and LXRα/ABCA1-regulated lipid raft reorganization in SK-N-MC cells. Sci Rep 2016; 6: 36746.
[http://dx.doi.org/10.1038/srep36746] [PMID: 27829662]
[29]
Baier L, Kovacs P, Wiedrich C, et al. Positional cloning of an obesity/diabetes susceptibility gene(s) on chromosome 11 in Pima Indians. Ann N Y Acad Sci 2002; 967: 258-64.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb04281.x] [PMID: 12079853]
[30]
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15(7): 539-53.
[http://dx.doi.org/10.1002/(SICI)1096-9136(199807)15:7<539:AID-DIA668>3.0.CO;2-S] [PMID: 9686693]
[31]
Portet F, Ousset PJ, Visser PJ, et al. MCI Working Group of the European Consortium on Alzheimer’s Disease (EADC). Mild cognitive impairment (MCI) in medical practice: a critical review of the concept and new diagnostic procedure. Report of the MCI Working Group of the European Consortium on Alzheimer’s Disease. J Neurol Neurosurg Psychiatry 2006; 77(6): 714-8.
[http://dx.doi.org/10.1136/jnnp.2005.085332] [PMID: 16549412]
[32]
Kim JD, Kang SJ, Lee MK, et al. C-peptide-based index is more related to incident type 2 diabetes in non-diabetic subjects than insulin-based index. Endocrinol Metab (Seoul) 2016; 31(2): 320-7.
[http://dx.doi.org/10.3803/EnM.2016.31.2.320] [PMID: 27349701]
[33]
Yu J, Li J, Huang X. The Beijing version of the Montreal Cognitive Assessment as a brief screening tool for mild cognitive impairment: A community-based study. BMC Psychiatry 2012; 12: 156.
[http://dx.doi.org/10.1186/1471-244X-12-156] [PMID: 23009126]
[34]
Chen X, Zhang R, Xiao Y, Dong J, Niu X, Kong W. reliability and validity of the beijing version of the montreal cognitive assessment in the evaluation of cognitive function of adult patients with OSAHS. PLoS One 2015; 10(7)e0132361
[http://dx.doi.org/10.1371/journal.pone.0132361] [PMID: 26208289]
[35]
Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005; 53(4): 695-9.
[http://dx.doi.org/10.1111/j.1532-5415.2005.53221.x] [PMID: 15817019]
[36]
Rakusa M, Jensterle J, Mlakar J. Clock drawing test: A simple scoring system for the accurate screening of cognitive impairment in patients with mild cognitive impairment and dementia. Dement Geriatr Cogn Disord 2018; 45(5-6): 326-34.
[http://dx.doi.org/10.1159/000490381] [PMID: 30036864]
[37]
Chen YL, Chen YH, Lieh-Mak F. Semantic verbal fluency deficit as a familial trait marker in schizophrenia. Psychiatry Res 2000; 95(2): 133-48.
[http://dx.doi.org/10.1016/S0165-1781(00)00166-9] [PMID: 10963799]
[38]
Chasles MJ, Tremblay A, Escudier F, et al. An examination of semantic impairment in amnestic mci and ad: What can we learn from verbal fluency? Arch Clin Neuropsychol 2019; 35(1): 22-30.
[39]
Zhao Q, Lv Y, Zhou Y, Hong Z, Guo Q. Short-term delayed recall of auditory verbal learning test is equivalent to long-term delayed recall for identifying amnestic mild cognitive impairment. PLoS One 2012; 7(12)e51157
[http://dx.doi.org/10.1371/journal.pone.0051157] [PMID: 23236445]
[40]
Lansbergen MM, Kenemans JL, van Engeland H. Stroop interference and attention-deficit/hyperactivity disorder: a review and meta-analysis. Neuropsychology 2007; 21(2): 251-62.
[http://dx.doi.org/10.1037/0894-4105.21.2.251] [PMID: 17402825]
[41]
Manzine PR, Souza MDS, Cominetti MR. BACE1 levels are increased in plasma of Alzheimer’s disease patients compared with matched cognitively healthy controls. Per Med 2016; 13(6): 531-40.
[http://dx.doi.org/10.2217/pme-2016-0033] [PMID: 29754550]
[42]
Busquets O, Ettcheto M, Pallàs M, et al. Long-term exposition to a high fat diet favors the appearance of β-amyloid depositions in the brain of C57BL/6J mice. A potential model of sporadic Alzheimer’s disease. Mech Ageing Dev 2017; 162: 38-45.
[http://dx.doi.org/10.1016/j.mad.2016.11.002] [PMID: 27863851]
[43]
Li S, Wang N, Lou J, Zhang X. Expression of β-site APP-cleaving enzyme 1 in the hippocampal tissue of an insulin-resistant rat model of Alzheimer’s disease. Exp Ther Med 2015; 9(6): 2389-93.
[http://dx.doi.org/10.3892/etm.2015.2391] [PMID: 26136993]
[44]
Hazan E, Frankenburg F, Brenkel M, Shulman K. The test of time: A history of clock drawing. Int J Geriatr Psychiatry 2018; 33(1): e22-30.
[http://dx.doi.org/10.1002/gps.4731] [PMID: 28556262]
[45]
Dugbartey AT, Rosenbaum JG, Sanchez PN, Townes BD. Neuropsychological assessment of executive functions. Semin Clin Neuropsychiatry 1999; 4(1): 5-12.
[PMID: 10229788]
[46]
Shen Y, Wang H, Sun Q, et al. Increased plasma beta-secretase 1 may predict conversion to Alzheimer’s disease dementia in individuals with mild cognitive impairment. Biol Psychiatry 2018; 83(5): 447-55.
[http://dx.doi.org/10.1016/j.biopsych.2017.02.007] [PMID: 28359566]
[47]
Westwood S, Liu B, Baird AL, et al. The influence of insulin resistance on cerebrospinal fluid and plasma biomarkers of Alzheimer’s pathology. Alzheimers Res Ther 2017; 9(1): 31.
[http://dx.doi.org/10.1186/s13195-017-0258-6] [PMID: 28441961]
[48]
Baranello RJ, Bharani KL, Padmaraju V, et al. Amyloid-beta protein clearance and degradation (ABCD) pathways and their role in Alzheimer’s disease. Curr Alzheimer Res 2015; 12(1): 32-46.
[http://dx.doi.org/10.2174/1567205012666141218140953] [PMID: 25523424]
[49]
Luck T, Riedel-Heller SG, Luppa M, et al. Apolipoprotein E epsilon 4 genotype and a physically active lifestyle in late life: Analysis of gene-environment interaction for the risk of dementia and Alzheimer’s disease dementia. Psychol Med 2014; 44(6): 1319-29.
[http://dx.doi.org/10.1017/S0033291713001918] [PMID: 23883793]

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