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当代阿耳茨海默病研究

Editor-in-Chief

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

General Research Article

AD小鼠模型中唾液Aβ分泌和口腔微生物组改变

卷 17, 期 12, 2020

页: [1133 - 1144] 页: 12

弟呕挨: 10.2174/1567205018666210119151952

价格: $65

摘要

背景:大脑中含有斑块聚集的β淀粉样蛋白(Aβ)肽是阿尔茨海默氏病(AD)的标志。但是,Aβ是由大脑外部的细胞类型产生的,这表明该肽可能具有广泛的生理用途。 目的:基于我们先前在淀粉样蛋白β前体蛋白(APP)在肠上皮中表达的研究成果,我们推测唾液上皮也可能表达APP,并且是Aβ的来源。 方法:为了开始验证这个想法,我们将人类年龄匹配的对照和AD唾液腺与C57BL / 6野生型,AppNL-G-F和APP / PS1小鼠进行了比较。 结果:雄性和雌性AD,AppNL-G-F和APP / PS1腺均显示出强大的APP和Aβ免疫反应性。与野生型和APP / PS1小鼠相比,雌性AppNL-G-F小鼠的毛果芸香碱刺激的Aβ1-42水平显着更高。未检测到男性唾液Aβ水平的差异。在任何一组中,总毛果芸香碱刺激的唾液量均未观察到显着差异。与野生型小鼠相比,雄性和雌性AppNL-G-F小鼠均未显示APP / PS1小鼠口腔微生物组门和属丰富度显着差异。雄性而非雌性APP / PS1和AppNL-G-F小鼠的磨牙釉质比野生型小鼠明显稀薄。 结论:这些数据支持以下观点:除唾液Aβ和口腔健康变化外,AD期间还存在口腔微生物组变化。

关键词: 微生物组,老年痴呆症,淀粉样蛋白,炎症,唾液,生物标志物。

« Previous
[1]
Haass C, Lemere CA, Capell A, et al. The Swedish mutation causes early-onset Alzheimer’s disease by beta-secretase cleavage within the secretory pathway. Nat Med 1995; 1(12): 1291-6.
[http://dx.doi.org/10.1038/nm1295-1291] [PMID: 7489411]
[2]
Evin G, Cappai R, Li QX, et al. Candidate gamma-secretases in the generation of the carboxyl terminus of the Alzheimer’s disease beta A4 amyloid: pPossible involvement of cathepsin D. Biochemistry 1995; 34(43): 14185-92.
[http://dx.doi.org/10.1021/bi00043a024] [PMID: 7578016]
[3]
Citron M, Teplow DB, Selkoe DJ. Generation of amyloid beta protein from its precursor is sequence specific. Neuron 1995; 14(3): 661-70.
[http://dx.doi.org/10.1016/0896-6273(95)90323-2] [PMID: 7695913]
[4]
Higaki J, Quon D, Zhong Z, Cordell B. Inhibition of beta-amyloid formation identifies proteolytic precursors and subcellular site of catabolism. Neuron 1995; 14(3): 651-9.
[http://dx.doi.org/10.1016/0896-6273(95)90322-4] [PMID: 7695912]
[5]
Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ. beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 1993; 268(5): 3021-4.
[http://dx.doi.org/10.1016/S0021-9258(18)53650-4] [PMID: 8428976]
[6]
Puig KL, Combs CK. Expression and function of APP and its metabolites outside the central nervous system. Exp Gerontol 2013; 48(7): 608-11.
[http://dx.doi.org/10.1016/j.exger.2012.07.009] [PMID: 22846461]
[7]
Akaaboune M, Allinquant B, Farza H, et al. Developmental regulation of amyloid precursor protein at the neuromuscular junction in mouse skeletal muscle. Mol Cell Neurosci 2000; 15(4): 355-67.
[http://dx.doi.org/10.1006/mcne.2000.0834] [PMID: 10845772]
[8]
Galloway S, Jian L, Johnsen R, Chew S, Mamo JC. Beta-amyloid or its precursor protein is found in epithelial cells of the small intestine and is stimulated by high-fat feeding. J Nutr Biochem 2007; 18(4): 279-84.
[http://dx.doi.org/10.1016/j.jnutbio.2006.07.003] [PMID: 16962759]
[9]
Herzog V, Kirfel G, Siemes C, Schmitz A. Biological roles of APP in the epidermis. Eur J Cell Biol 2004; 83(11-12): 613-24.
[http://dx.doi.org/10.1078/0171-9335-00401] [PMID: 15679106]
[10]
Lee YH, Tharp WG, Maple RL, Nair S, Permana PA, Pratley RE. Amyloid precursor protein expression is upregulated in adipocytes in obesity. Obesity (Silver Spring) 2008; 16(7): 1493-500.
[http://dx.doi.org/10.1038/oby.2008.267] [PMID: 18483477]
[11]
Sandbrink R, Masters CL, Beyreuther K. Beta A4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons. J Biol Chem 1994; 269(2): 1510-7.
[http://dx.doi.org/10.1016/S0021-9258(17)42286-1] [PMID: 8288617]
[12]
Selkoe DJ, Podlisny MB, Joachim CL, et al. Beta-amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci USA 1988; 85(19): 7341-5.
[http://dx.doi.org/10.1073/pnas.85.19.7341] [PMID: 3140239]
[13]
Yamada T, Sasaki H, Dohura K, Goto I, Sakaki Y. Structure and expression of the alternatively-spliced forms of mRNA for the mouse homolog of Alzheimer’s disease amyloid beta protein precursor. Biochem Biophys Res Commun 1989; 158(3): 906-12.
[http://dx.doi.org/10.1016/0006-291X(89)92808-8] [PMID: 2493250]
[14]
Puig KL, Lutz BM, Urquhart SA, et al. Overexpression of mutant amyloid-β protein precursor and presenilin 1 modulates enteric nervous system. J Alzheimers Dis 2015; 44(4): 1263-78.
[http://dx.doi.org/10.3233/JAD-142259] [PMID: 25408221]
[15]
Puig KL, Manocha GD, Combs CK. Amyloid precursor protein mediated changes in intestinal epithelial phenotype in vitro. PLoS One 2015; 10(3)e0119534
[http://dx.doi.org/10.1371/journal.pone.0119534] [PMID: 25742317]
[16]
Ashton NJ, Ide M, Schöll M, et al. No association of salivary total tau concentration with Alzheimer’s disease. Neurobiol Aging 2018; 70: 125-7.
[http://dx.doi.org/10.1016/j.neurobiolaging.2018.06.014] [PMID: 30007161]
[17]
Pekeles H, Qureshi HY, Paudel HK, Schipper HM, Gornistky M, Chertkow H. Development and validation of a salivary tau biomarker in Alzheimer’s disease. Alzheimer’s Demen (Amsterdam, Netherlands) 2019; 11: 53-60.
[18]
Shi M, Sui YT, Peskind ER, et al. Salivary tau species are potential biomarkers of Alzheimer’s disease. J Alzheimers Dis 2011; 27(2): 299-305.
[http://dx.doi.org/10.3233/JAD-2011-110731] [PMID: 21841250]
[19]
Bermejo-Pareja F, Antequera D, Vargas T, Molina JA, Carro E. Saliva levels of Abeta1-42 as potential biomarker of Alzheimer’s disease: a pilot study. BMC Neurol 2010; 10: 108.
[http://dx.doi.org/10.1186/1471-2377-10-108] [PMID: 21047401]
[20]
Lee M, Guo JP, Kennedy K, McGeer EG, McGeer PL. A method for diagnosing Alzheimer’s disease based on salivary amyloid-β protein 42 levels. J Alzheimers Dis 2017; 55(3): 1175-82.
[http://dx.doi.org/10.3233/JAD-160748] [PMID: 27792013]
[21]
Sabbagh MN, Shi J, Lee M, et al. Salivary beta amyloid protein levels are detectable and differentiate patients with Alzheimer’s disease dementia from normal controls: Preliminary findings. BMC Neurol 2018; 18(1): 155.
[http://dx.doi.org/10.1186/s12883-018-1160-y] [PMID: 30257642]
[22]
Figueira J, Jonsson P, Nordin Adolfsson A, et al. NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls. Mol Biosyst 2016; 12(8): 2562-71.
[http://dx.doi.org/10.1039/C6MB00233A] [PMID: 27265744]
[23]
Huan T, Tran T, Zheng J, et al. Metabolomics analyses of saliva detect novel biomarkers of Alzheimer’s disease. J Alzheimers Dis 2018; 65(4): 1401-16.
[http://dx.doi.org/10.3233/JAD-180711] [PMID: 30175979]
[24]
Ralbovsky NM, Halámková L, Wall K, Anderson-Hanley C, Lednev IK. Screening for Alzheimer’s disease using saliva: a new approach based on machine learning and Raman hyperspectroscopy. J Alzheimers Dis 2019; 71(4): 1351-9.
[http://dx.doi.org/10.3233/JAD-190675] [PMID: 31524171]
[25]
Yilmaz A, Geddes T, Han B, et al. Diagnostic biomarkers of Alzheimer’s disease as identified in saliva using 1H NMR-based metabolomics. J Alzheimers Dis 2017; 58(2): 355-9.
[http://dx.doi.org/10.3233/JAD-161226] [PMID: 28453477]
[26]
Aragón F, Zea-Sevilla MA, Montero J, et al. Oral health in Alzheimer’s disease: A multicenter case-control study. Clin Oral Investig 2018; 22(9): 3061-70.
[http://dx.doi.org/10.1007/s00784-018-2396-z] [PMID: 29476334]
[27]
Ship JA, DeCarli C, Friedland RP, Baum BJ. Diminished submandibular salivary flow in dementia of the Alzheimer type. J Gerontol 1990; 45(2): M61-6.
[http://dx.doi.org/10.1093/geronj/45.2.M61] [PMID: 2313044]
[28]
Kalia M. Dysphagia and aspiration pneumonia in patients with Alzheimer’s disease. Metabolism 2003; 52(10): 36-8.
[http://dx.doi.org/10.1016/S0026-0495(03)00300-7] [PMID: 14577062]
[29]
Scannapieco FA, Cantos A. Oral inflammation and infection, and chronic medical diseases: Implications for the elderly. Periodontol 2000 2016; 72(1): 153-75.
[http://dx.doi.org/10.1111/prd.12129] [PMID: 27501498]
[30]
Chen CK, Wu YT, Chang YC. Association between chronic periodontitis and the risk of Alzheimer’s disease: A retrospective, population-based, matched-cohort study. Alzheimers Res Ther 2017; 9(1): 56.
[http://dx.doi.org/10.1186/s13195-017-0282-6] [PMID: 28784164]
[31]
Foley NC, Affoo RH, Siqueira WL, Martin RE. A systematic review examining the oral health status of persons with dementia. JDR Clin Trans Res 2017; 2(4): 330-42.
[http://dx.doi.org/10.1177/2380084417714789] [PMID: 30931751]
[32]
Hatipoglu MG, Kabay SC, Güven G. The clinical evaluation of the oral status in Alzheimer-type dementia patients. Gerodontology 2011; 28(4): 302-6.
[http://dx.doi.org/10.1111/j.1741-2358.2010.00401.x] [PMID: 21054507]
[33]
Holmer J, Eriksdotter M, Schultzberg M, Pussinen PJ, Buhlin K. Association between periodontitis and risk of Alzheimer’s disease, mild cognitive impairment and subjective cognitive decline: A case-control study. J Clin Periodontol 2018; 45(11): 1287-98.
[http://dx.doi.org/10.1111/jcpe.13016] [PMID: 30289998]
[34]
Ide M, Harris M, Stevens A, et al. Periodontitis and cognitive decline in Alzheimer’s disease. PLoS One 2016; 11(3)e0151081
[http://dx.doi.org/10.1371/journal.pone.0151081] [PMID: 26963387]
[35]
Leira Y, Domínguez C, Seoane J, et al. iIs periodontal disease associated with Alzheimer’s disease? a systematic review with meta-analysis. Neuroepidemiology 2017; 48(1-2): 21-31.
[http://dx.doi.org/10.1159/000458411] [PMID: 28219071]
[36]
Martande SS, Pradeep AR, Singh SP, et al. Periodontal health condition in patients with Alzheimer’s disease. Am J Alzheimers Dis Other Demen 2014; 29(6): 498-502.
[http://dx.doi.org/10.1177/1533317514549650] [PMID: 25214647]
[37]
Minn YK, Suk SH, Park H, et al. Tooth loss is associated with brain white matter change and silent infarction among adults without dementia and stroke. J Korean Med Sci 2013; 28(6): 929-33.
[http://dx.doi.org/10.3346/jkms.2013.28.6.929] [PMID: 23772160]
[38]
Okamoto N, Morikawa M, Tomioka K, Yanagi M, Amano N, Kurumatani N. Association between tooth loss and the development of mild memory impairment in the elderly: The Fujiwara-kyo Study. J Alzheimers Dis 2015; 44(3): 777-86.
[http://dx.doi.org/10.3233/JAD-141665] [PMID: 25362033]
[39]
Oue H, Miyamoto Y, Koretake K, et al. Tooth loss might not alter molecular pathogenesis in an aged transgenic Alzheimer’s disease model mouse. Gerodontology 2016; 33(3): 308-14.
[http://dx.doi.org/10.1111/ger.12153] [PMID: 25243637]
[40]
Oue H, Miyamoto Y, Okada S, et al. Tooth loss induces memory impairment and neuronal cell loss in APP transgenic mice. Behav Brain Res 2013; 252: 318-25.
[http://dx.doi.org/10.1016/j.bbr.2013.06.015] [PMID: 23773908]
[41]
Takeuchi K, Ohara T, Furuta M, et al. Tooth loss and risk of dementia in the community: The Hisayama Study. J Am Geriatr Soc 2017; 65(5): e95-e100.
[http://dx.doi.org/10.1111/jgs.14791] [PMID: 28272750]
[42]
Tiisanoja A, Syrjala AM, Tertsonen M, et al. Oral diseases and inflammatory burden and Alzheimer's disease among subjects aged 75 years or older Oral diseases and inflammatory burden and Alzheimer's disease among subjects aged 75 years or older 2019; 39(2): 158-65.
[http://dx.doi.org/10.1111/scd.12357]
[43]
Kamer AR, Pirraglia E, Tsui W, et al. Periodontal disease associates with higher brain amyloid load in normal elderly. Neurobiol Aging 2015; 36(2): 627-33.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.10.038] [PMID: 25491073]
[44]
Saito T, Matsuba Y, Mihira N, et al. Single App knock-in mouse models of Alzheimer’s disease. Nat Neurosci 2014; 17(5): 661-3.
[http://dx.doi.org/10.1038/nn.3697] [PMID: 24728269]
[45]
Kumar DK, Choi SH, Washicosky KJ, et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Sci Transl Med 2016; 8(340)340ra72
[http://dx.doi.org/10.1126/scitranslmed.aaf1059] [PMID: 27225182]
[46]
Moir RD, Lathe R, Tanzi RE. The antimicrobial protection hypothesis of Alzheimer’s disease. Alzheimers Dement 2018; 14(12): 1602-14.
[http://dx.doi.org/10.1016/j.jalz.2018.06.3040] [PMID: 30314800]
[47]
Soscia SJ, Kirby JE, Washicosky KJ, et al. The Alzheimer’s disease-associated amyloid beta-protein is an antimicrobial peptide. PLoS One 2010; 5(3)e9505
[http://dx.doi.org/10.1371/journal.pone.0009505] [PMID: 20209079]
[48]
Akbari E, Asemi Z, Daneshvar Kakhaki R, et al. Effect of probiotic supplementation on cognitive function and metabolic status in alzheimer’s disease: A randomized, double-blind and controlled trial. Front Aging Neurosci 2016; 8: 256.
[http://dx.doi.org/10.3389/fnagi.2016.00256] [PMID: 27891089]
[49]
Nimgampalle M, Kuna Y. Anti-Alzheimer properties of probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer’s disease induced albino rats. J Clin Diagn Res 2017; 11(8): KC01-5.
[http://dx.doi.org/10.7860/JCDR/2017/26106.10428] [PMID: 28969160]
[50]
Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: How gut microbes shape human behavior. J Psychiatr Res 2015; 63: 1-9.
[http://dx.doi.org/10.1016/j.jpsychires.2015.02.021] [PMID: 25772005]
[51]
Vogt NM, Kerby RL, Dill-McFarland KA, et al. Gut microbiome alterations in Alzheimer’s disease. Sci Rep 2017; 7(1): 13537.
[http://dx.doi.org/10.1038/s41598-017-13601-y] [PMID: 29051531]
[52]
Balin BJ, Little CS, Hammond CJ, et al. Chlamydophila pneumoniae and the etiology of late-onset Alzheimer’s disease. J Alzheimers Dis 2008; 13(4): 371-80.
[http://dx.doi.org/10.3233/JAD-2008-13403] [PMID: 18487846]
[53]
Harach T, Marungruang N, Duthilleul N, et al. Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep 2017; 7: 41802.
[http://dx.doi.org/10.1038/srep41802] [PMID: 28176819]
[54]
Pistollato F, Sumalla Cano S, et al. Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr Rev 2016; 74(10): 624-34.
[http://dx.doi.org/10.1093/nutrit/nuw023] [PMID: 27634977]
[55]
Austin SA, Combs CK. Amyloid precursor protein mediates monocyte adhesion in AD tissue and apoE(-)/(-) mice. Neurobiol Aging 2010; 31(11): 1854-66.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.10.013] [PMID: 19058878]
[56]
Wu SC, Cao ZS, Chang KM, Juang JL. Intestinal microbial dysbiosis aggravates the progression of Alzheimer’s disease in Drosophila. Nat Commun 2017; 8(1): 24.
[http://dx.doi.org/10.1038/s41467-017-00040-6] [PMID: 28634323]
[57]
Shimizu K, Hanaoka Y, Akama T, Kono I. Ageing and free-living daily physical activity effects on salivary beta-defensin 2 secretion. J Sports Sci 2017; 35(7): 617-23.
[http://dx.doi.org/10.1080/02640414.2016.1182640] [PMID: 27237844]
[58]
Gillum TL, Kuennen MR, Castillo MN, Williams NL, Jordan-Patterson AT. Exercise, but not acute sleep loss, increases salivary antimicrobial protein secretion. J Strength Cond Res 2015; 29(5): 1359-66.
[http://dx.doi.org/10.1519/JSC.0000000000000828] [PMID: 25915527]
[59]
Malcolm J, Sherriff A, Lappin DF, et al. Salivary antimicrobial proteins associate with age-related changes in streptococcal composition in dental plaque. Mol Oral Microbiol 2014; 29(6): 284-93.
[http://dx.doi.org/10.1111/omi.12058] [PMID: 24890264]
[60]
Jourdain ML, Velard F, Pierrard L, Sergheraert J, Gangloff SC, Braux J. Cationic antimicrobial peptides and periodontal physiopathology: A systematic review. J Periodontal Res 2019; 54(6): 589-600.
[http://dx.doi.org/10.1111/jre.12676] [PMID: 31215656]
[61]
Manocha GD, Floden AM, Miller NM, et al. Temporal progression of Alzheimer’s disease in brains and intestines of transgenic mice. Neurobiol Aging 2019; 81: 166-76.
[http://dx.doi.org/10.1016/j.neurobiolaging.2019.05.025] [PMID: 31284126]
[62]
Sanz M, Beighton D, Curtis MA, et al. Role of microbial biofilms in the maintenance of oral health and in the development of dental caries and periodontal diseases. Consensus report of group 1 of the Joint EFP/ORCA workshop on the boundaries between caries and periodontal disease. J Clin Periodontol 2017; 44(18): S5-S11.
[http://dx.doi.org/10.1111/jcpe.12682] [PMID: 28266109]
[63]
Sakurai K, Wang D, Suzuki J, et al. High incidence of actinobacillus actinomycetemcomitans infection in acute coronary syndrome. Int Heart J 2007; 48(6): 663-75.
[http://dx.doi.org/10.1536/ihj.48.663] [PMID: 18160759]
[64]
Fine DH, Furgang D, Goldman D. Saliva from subjects harboring Actinobacillus actinomycetemcomitans kills Streptococcus mutans in vitro. J Periodontol 2007; 78(3): 518-26.
[http://dx.doi.org/10.1902/jop.2007.060229] [PMID: 17335376]
[65]
Litvak Y, Byndloss MX, Bäumler AJ. Colonocyte metabolism shapes the gut microbiota. Science 2018; 362(6418)eaat9076
[http://dx.doi.org/10.1126/science.aat9076] [PMID: 30498100]
[66]
Ilievski V, Zuchowska PK, Green SJ, et al. Chronic oral application of a periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice. PLoS One 2018; 13(10)e0204941
[http://dx.doi.org/10.1371/journal.pone.0204941] [PMID: 30281647]

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