請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78344完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳漪紋(Yi-Wen Chen) | |
| dc.contributor.author | Kuan-Lun Fu | en |
| dc.contributor.author | 傅冠綸 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:52:13Z | - |
| dc.date.available | 2025-08-01 | |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-07 | |
| dc.identifier.citation | 1. Organization, W.H. https://www.who.int/news-room/fact-sheets/detail/dementia. 2. 2018 Alzheimer's disease facts and figures. Alzheimer's Dementia, 2018. 14(3): p. 367-429. 3. Chu, L.W., Alzheimer's disease: early diagnosis and treatment. Hong Kong Med J, 2012. 18(3): p. 228-37. 4. International., A.s.D., World Alzheimer Report 2019: Attitudes to dementia. London: Alzheimer's Disease International. 2019. . 5. 2020 Alzheimer's disease facts and figures. Alzheimers Dement, 2020. 6. Du, X., X. Wang, and M. Geng, Alzheimer's disease hypothesis and related therapies. Transl Neurodegener, 2018. 7: p. 2. 7. Hardy, J. and D.J. Selkoe, The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 2002. 297(5580): p. 353-6. 8. Pákáski, M. and J. Kálmán, Interactions between the amyloid and cholinergic mechanisms in Alzheimer's disease. Neurochem Int, 2008. 53(5): p. 103-11. 9. Zhang, Y., et al., Selective cytotoxicity of intracellular amyloid beta peptide1-42 through p53 and Bax in cultured primary human neurons. J Cell Biol, 2002. 156(3): p. 519-29. 10. Tanzi, R.E., A brief history of Alzheimer's disease gene discovery. J Alzheimers Dis, 2013. 33 Suppl 1: p. S5-13. 11. Cummings, J., et al., Drug development in Alzheimer's disease: the path to 2025. Alzheimers Res Ther, 2016. 8: p. 39. 12. Bolos, M., J.R. Perea, and J. Avila, Alzheimer's disease as an inflammatory disease. Biomol Concepts, 2017. 8(1): p. 37-43. 13. Mudher, A. and S. Lovestone, Alzheimer's disease-do tauists and baptists finally shake hands? Trends Neurosci, 2002. 25(1): p. 22-6. 14. Francis, P.T., et al., The cholinergic hypothesis of Alzheimer's disease: a review of progress. J Neurol Neurosurg Psychiatry, 1999. 66(2): p. 137-47. 15. Contestabile, A., The history of the cholinergic hypothesis. Behavioural Brain Research, 2011. 221(2): p. 334-340. 16. Aliev, G., et al., The role of oxidative stress in the pathophysiology of cerebrovascular lesions in Alzheimer's disease. Brain Pathol, 2002. 12(1): p. 21-35. 17. Moore, A.H. and M.K. O'Banion, Neuroinflammation and anti-inflammatory therapy for Alzheimer's disease. Adv Drug Deliv Rev, 2002. 54(12): p. 1627-56. 18. Ballatore, C., V.M. Lee, and J.Q. Trojanowski, Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat Rev Neurosci, 2007. 8(9): p. 663-72. 19. Tuppo, E.E. and H.R. Arias, The role of inflammation in Alzheimer's disease. Int J Biochem Cell Biol, 2005. 37(2): p. 289-305. 20. Yaari, R., A.S. Fleisher, and P.N. Tariot, Updates to diagnostic guidelines for Alzheimer's disease. The primary care companion for CNS disorders, 2011. 13(5): p. PCC.11f01262. 21. Ray, S., et al., Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med, 2007. 13(11): p. 1359-62. 22. Schneider, P., H. Hampel, and K. Buerger, Biological marker candidates of Alzheimer's disease in blood, plasma, and serum. CNS Neurosci Ther, 2009. 15(4): p. 358-74. 23. O'Bryant, S.E., et al., A blood-based algorithm for the detection of Alzheimer's disease. Dement Geriatr Cogn Disord, 2011. 32(1): p. 55-62. 24. O'Brien, J.T., Role of imaging techniques in the diagnosis of dementia. Br J Radiol, 2007. 80 Spec No 2: p. S71-7. 25. Morris, J.C., et al., Mild cognitive impairment represents early-stage alzheimer disease. Archives of Neurology, 2001. 58(3): p. 397-405. 26. 台灣衛生福利部、社團法人台灣失智症協會, 失智症診療手冊. 2016. 27. Morris, J.C., et al., Clinical dementia rating training and reliability in multicenter studies: the Alzheimer's Disease Cooperative Study experience. Neurology, 1997. 48(6): p. 1508-10. 28. Martin, C.R., et al., The Brain-Gut-Microbiome Axis. Cellular and molecular gastroenterology and hepatology, 2018. 6(2): p. 133-148. 29. Structure, function and diversity of the healthy human microbiome. Nature, 2012. 486(7402): p. 207-14. 30. Belkaid, Y. and O.J. Harrison, Homeostatic Immunity and the Microbiota. Immunity, 2017. 46(4): p. 562-576. 31. O'Mahony, S.M., et al., Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res, 2015. 277: p. 32-48. 32. Browning, K.N., S. Verheijden, and G.E. Boeckxstaens, The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation. Gastroenterology, 2017. 152(4): p. 730-744. 33. Zhao, Y., P. Dua, and W.J. Lukiw, Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer's Disease (AD). J Alzheimers Dis Parkinsonism, 2015. 5(1): p. 177. 34. Szablewski, L., Human Gut Microbiota in Health and Alzheimer's Disease. J Alzheimers Dis, 2018. 62(2): p. 549-560. 35. Mayer, E.A., K. Tillisch, and A. Gupta, Gut/brain axis and the microbiota. J Clin Invest, 2015. 125(3): p. 926-38. 36. Schwartz, K. and B.R. Boles, Microbial amyloids--functions and interactions within the host. Curr Opin Microbiol, 2013. 16(1): p. 93-9. 37. Dzidic, M., et al., Oral microbiome development during childhood: an ecological succession influenced by postnatal factors and associated with tooth decay. The ISME Journal, 2018. 12(9): p. 2292-2306. 38. Shang, F.-M. and H.-L. Liu, Fusobacterium nucleatum and colorectal cancer: A review. World journal of gastrointestinal oncology, 2018. 10(3): p. 71-81. 39. Bell, J.S., et al., From Nose to Gut - The Role of the Microbiome in Neurological Disease. Neuropathol Appl Neurobiol, 2018. 40. Gao, L., et al., Oral microbiomes: more and more importance in oral cavity and whole body. Protein Cell, 2018. 41. Cagnin, A., et al., In-vivo measurement of activated microglia in dementia. Lancet, 2001. 358(9280): p. 461-7. 42. Llorens, F., et al., Cerebrospinal Fluid Biomarkers of Alzheimer's Disease Show Different but Partially Overlapping Profile Compared to Vascular Dementia. Front Aging Neurosci, 2017. 9: p. 289. 43. Kinney, J.W., et al., Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement (N Y), 2018. 4: p. 575-590. 44. Zhang, F., et al., Acute Hypoxia Induced an Imbalanced M1/M2 Activation of Microglia through NF-κB Signaling in Alzheimer’s Disease Mice and Wild-Type Littermates. Frontiers in Aging Neuroscience, 2017. 9(282). 45. Ojala, J., et al., Expression of interleukin-18 is increased in the brains of Alzheimer's disease patients. Neurobiol Aging, 2009. 30(2): p. 198-209. 46. Holmes, C., et al., Systemic inflammation and disease progression in Alzheimer disease. Neurology, 2009. 73(10): p. 768-774. 47. Capuron, L. and A.H. Miller, Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther, 2011. 130(2): p. 226-38. 48. Rosen, W.G., R.C. Mohs, and K.L. Davis, A new rating scale for Alzheimer's disease. Am J Psychiatry, 1984. 141(11): p. 1356-64. 49. Takuma, K., et al., RAGE-mediated signaling contributes to intraneuronal transport of amyloid-beta and neuronal dysfunction. Proc Natl Acad Sci U S A, 2009. 106(47): p. 20021-6. 50. Park, K.M. and W.J. Bowers, Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction. Cell Signal, 2010. 22(7): p. 977-83. 51. Kitazawa, M., et al., Blocking IL-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal β-catenin pathway function in an Alzheimer's disease model. J Immunol, 2011. 187(12): p. 6539-49. 52. Spooren, A., et al., Interleukin-6, a mental cytokine. Brain Res Rev, 2011. 67(1-2): p. 157-83. 53. Sutinen, E.M., et al., Pro-inflammatory interleukin-18 increases Alzheimer's disease-associated amyloid-β production in human neuron-like cells. J Neuroinflammation, 2012. 9: p. 199. 54. Hung, Y.-N., et al., The epidemiology and burden of Alzheimer's disease in Taiwan utilizing data from the National Health Insurance Research Database. ClinicoEconomics and outcomes research : CEOR, 2016. 8: p. 387-395. 55. Chen, T.-B., et al., Comorbidity and dementia: A nationwide survey in Taiwan. PloS one, 2017. 12(4): p. e0175475-e0175475. 56. Cechetto, D.F., V. Hachinski, and S.N. Whitehead, Vascular risk factors and Alzheimer's disease. Expert Rev Neurother, 2008. 8(5): p. 743-50. 57. Kamer, A.R., et al., Alzheimer's disease and peripheral infections: the possible contribution from periodontal infections, model and hypothesis. J Alzheimers Dis, 2008. 13(4): p. 437-49. 58. Kodl, C.T. and E.R. Seaquist, Cognitive dysfunction and diabetes mellitus. Endocr Rev, 2008. 29(4): p. 494-511. 59. Qiu, C., D. De Ronchi, and L. Fratiglioni, The epidemiology of the dementias: an update. Curr Opin Psychiatry, 2007. 20(4): p. 380-5. 60. Luchsinger, J.A., Adiposity, hyperinsulinemia, diabetes and Alzheimer's disease: an epidemiological perspective. Eur J Pharmacol, 2008. 585(1): p. 119-29. 61. Licastro, F., et al., Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain? J Neuroimmunol, 2000. 103(1): p. 97-102. 62. Silva, M.V.F., et al., Alzheimer’s disease: risk factors and potentially protective measures. Journal of Biomedical Science, 2019. 26(1): p. 33. 63. Ballard, C., et al., Alzheimer's disease. Lancet, 2011. 377(9770): p. 1019-31. 64. Giri, M., M. Zhang, and Y. Lü, Genes associated with Alzheimer's disease: an overview and current status. Clin Interv Aging, 2016. 11: p. 665-81. 65. Karch, C.M. and A.M. Goate, Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry, 2015. 77(1): p. 43-51. 66. Liu, W., et al., Cerebrovascular disease, amyloid plaques, and dementia. Stroke, 2015. 46(5): p. 1402-7. 67. Skoog, I., et al., 15-year longitudinal study of blood pressure and dementia. Lancet, 1996. 347(9009): p. 1141-5. 68. Li, X., D. Song, and S.X. Leng, Link between type 2 diabetes and Alzheimer's disease: from epidemiology to mechanism and treatment. Clinical interventions in aging, 2015. 10: p. 549-560. 69. Kim, J., J.M. Basak, and D.M. Holtzman, The role of apolipoprotein E in Alzheimer's disease. Neuron, 2009. 63(3): p. 287-303. 70. Profenno, L.A., A.P. Porsteinsson, and S.V. Faraone, Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry, 2010. 67(6): p. 505-12. 71. Anstey, K.J., et al., Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies. Obes Rev, 2011. 12(5): p. e426-37. 72. Popp, J., et al., Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease. Biochem Pharmacol, 2013. 86(1): p. 37-42. 73. Xue-Shan, Z., et al., Imbalanced cholesterol metabolism in Alzheimer's disease. Clin Chim Acta, 2016. 456: p. 107-114. 74. Song, Y., et al., Association of statin use with risk of dementia: a meta-analysis of prospective cohort studies. Geriatr Gerontol Int, 2013. 13(4): p. 817-24. 75. McGuinness, B., et al., Statins for the prevention of dementia. Cochrane Database Syst Rev, 2016(1): p. Cd003160. 76. Håkansson, K., et al., Association between mid-life marital status and cognitive function in later life: population based cohort study. Bmj, 2009. 339: p. b2462. 77. Ray, B., et al., Restraint stress and repeated corticotrophin-releasing factor receptor activation in the amygdala both increase amyloid-β precursor protein and amyloid-β peptide but have divergent effects on brain-derived neurotrophic factor and pre-synaptic proteins in the prefrontal cortex of rats. Neuroscience, 2011. 184: p. 139-50. 78. Huang, C.W., et al., Elevated basal cortisol level predicts lower hippocampal volume and cognitive decline in Alzheimer's disease. J Clin Neurosci, 2009. 16(10): p. 1283-6. 79. Ownby, R.L., et al., Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Archives of general psychiatry, 2006. 63(5): p. 530-538. 80. Proserpio, P., et al., Integrating Sleep and Alzheimer's Disease Pathophysiology: Hints for Sleep Disorders Management. J Alzheimers Dis, 2018. 63(3): p. 871-886. 81. Cataldo, J.K., J.J. Prochaska, and S.A. Glantz, Cigarette smoking is a risk factor for Alzheimer's Disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis, 2010. 19(2): p. 465-80. 82. Schrijvers, E.M., et al., Associations of serum cortisol with cognitive function and dementia: the Rotterdam Study. J Alzheimers Dis, 2011. 25(4): p. 671-7. 83. Byers, A.L. and K. Yaffe, Depression and risk of developing dementia. Nat Rev Neurol, 2011. 7(6): p. 323-31. 84. Shen, L. and H.F. Ji, Vitamin D deficiency is associated with increased risk of Alzheimer's disease and dementia: evidence from meta-analysis. Nutr J, 2015. 14: p. 76. 85. de Wilde, M.C., et al., Lower brain and blood nutrient status in Alzheimer's disease: Results from meta-analyses. Alzheimers Dement (N Y), 2017. 3(3): p. 416-431. 86. Jin, L.J., et al., Global oral health inequalities: task group--periodontal disease. Adv Dent Res, 2011. 23(2): p. 221-6. 87. Liu, Y., et al., Infection of microglia with Porphyromonas gingivalis promotes cell migration and an inflammatory response through the gingipain-mediated activation of protease-activated receptor-2 in mice. Scientific Reports, 2017. 7(1): p. 11759. 88. Lai, H., et al., A prediction model for periodontal disease: modelling and validation from a National Survey of 4061 Taiwanese adults. J Clin Periodontol, 2015. 42(5): p. 413-21. 89. Grossi, S.G., et al., Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol, 1994. 65(3): p. 260-7. 90. Cekici, A., et al., Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontology 2000, 2014. 64(1): p. 57-80. 91. Meyle, J. and I. Chapple, Molecular aspects of the pathogenesis of periodontitis. Periodontology 2000, 2015. 69(1): p. 7-17. 92. Slots, J., Human viruses in periodontitis. Periodontology 2000, 2010. 53(1): p. 89-110. 93. Page, R.C. and H.E. Schroeder, Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest, 1976. 34(3): p. 235-49. 94. Page, R.C. and K.S. Kornman, The pathogenesis of human periodontitis: an introduction. Periodontology 2000, 1997. 14(1): p. 9-11. 95. Socransky, S.S., et al., Microbial complexes in subgingival plaque. Journal of Clinical Periodontology, 1998. 25(2): p. 134-144. 96. Von Troil-Lindén, B., et al., Periodontal findings in spouses. Journal of Clinical Periodontology, 1995. 22(2): p. 93-99. 97. Tonetti, M.S. and T.E. Van Dyke, Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Periodontol, 2013. 84(4 Suppl): p. S24-9. 98. Caton, J.G., et al., A new classification scheme for periodontal and peri-implant diseases and conditions – Introduction and key changes from the 1999 classification. Journal of Clinical Periodontology, 2018. 45(S20): p. S1-S8. 99. Tonetti, M.S., H. Greenwell, and K.S. Kornman, Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. Journal of Periodontology, 2018. 89(S1): p. S159-S172. 100. Socransky, S.S., et al., Microbial complexes in subgingival plaque. J Clin Periodontol, 1998. 25(2): p. 134-44. 101. Chen, C., et al., Oral microbiota of periodontal health and disease and their changes after nonsurgical periodontal therapy. The ISME Journal, 2018. 12(5): p. 1210-1224. 102. Patini, R., et al., Relationship between oral microbiota and periodontal disease: a systematic review. Eur Rev Med Pharmacol Sci, 2018. 22(18): p. 5775-5788. 103. Olsen, I. and K. Yamazaki, Can oral bacteria affect the microbiome of the gut? Journal of oral microbiology, 2019. 11(1): p. 1586422-1586422. 104. Segata, N., et al., Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol, 2012. 13(6): p. R42. 105. Arimatsu, K., et al., Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep, 2014. 4: p. 4828. 106. Okada, H. and S. Murakami, Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med, 1998. 9(3): p. 248-66. 107. Garlet, G.P., Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res, 2010. 89(12): p. 1349-63. 108. Prabhu, A., B.S. Michalowicz, and A. Mathur, Detection of local and systemic cytokines in adult periodontitis. J Periodontol, 1996. 67(5): p. 515-22. 109. Zekeridou, A., et al., Systemic inflammatory burden and local inflammation in periodontitis: What is the link between inflammatory biomarkers in serum and gingival crevicular fluid? Clinical and Experimental Dental Research, 2019. 5(2): p. 128-135. 110. D'Aiuto, F., et al., Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res, 2004. 83(2): p. 156-60. 111. Van Dyke, T.E. and D. Sheilesh, Risk factors for periodontitis. Journal of the International Academy of Periodontology, 2005. 7(1): p. 3-7. 112. Bui, F.Q., et al., Association between periodontal pathogens and systemic disease. Biomedical Journal, 2019. 42(1): p. 27-35. 113. Kellesarian, S.V., et al., Association Between Periodontal Disease and Erectile Dysfunction: A Systematic Review. American journal of men's health, 2018. 12(2): p. 338-346. 114. Winning, L. and G.J. Linden, Periodontitis and systemic disease. BDJ Team, 2015. 2(10): p. 15163. 115. Negrato, C.A., et al., Periodontal disease and diabetes mellitus. Journal of applied oral science : revista FOB, 2013. 21(1): p. 1-12. 116. Simpson, T.C., et al., Treatment of periodontal disease for glycaemic control in people with diabetes. Cochrane Database Syst Rev, 2010(5): p. Cd004714. 117. Borojevic, T., Smoking and periodontal disease. Materia socio-medica, 2012. 24(4): p. 274-276. 118. Taylor, G.W., et al., Severe periodontitis and risk for poor glycemic control in patients with non-insulin-dependent diabetes mellitus. J Periodontol, 1996. 67(10 Suppl): p. 1085-93. 119. Tonetti, M.S., Periodontitis and risk for atherosclerosis: an update on intervention trials. J Clin Periodontol, 2009. 36 Suppl 10: p. 15-9. 120. Renvert, S., et al., Osteoporosis and periodontitis in older subjects participating in the Swedish National Survey on Aging and Care (SNAC-Blekinge). Acta Odontol Scand, 2011. 69(4): p. 201-7. 121. Katz, J., et al., Inflammation, periodontitis, and coronary heart disease. Lancet, 2001. 358(9297): p. 1998. 122. Mercado, F., et al., Is there a relationship between rheumatoid arthritis and periodontal disease? J Clin Periodontol, 2000. 27(4): p. 267-72. 123. Singhrao, S.K., et al., Oral inflammation, tooth loss, risk factors, and association with progression of Alzheimer's disease. J Alzheimers Dis, 2014. 42(3): p. 723-37. 124. Chen, C.K., Y.T. Wu, and Y.C. Chang, Association between chronic periodontitis and the risk of Alzheimer's disease: a retrospective, population-based, matched-cohort study. Alzheimers Res Ther, 2017. 9(1): p. 56. 125. Sharp, E.S. and M. Gatz, Relationship between education and dementia: an updated systematic review. Alzheimer disease and associated disorders, 2011. 25(4): p. 289-304. 126. Holmer, J., et al., 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): p. 1287-1298. 127. Riviere, G.R., K.H. Riviere, and K.S. Smith, Molecular and immunological evidence of oral Treponema in the human brain and their association with Alzheimer's disease. Oral Microbiol Immunol, 2002. 17(2): p. 113-8. 128. Poole, S., et al., Determining the presence of periodontopathic virulence factors in short-term postmortem Alzheimer's disease brain tissue. J Alzheimers Dis, 2013. 36(4): p. 665-77. 129. Poole, S., et al., Active invasion of Porphyromonas gingivalis and infection-induced complement activation in ApoE-/- mice brains. J Alzheimers Dis, 2015. 43(1): p. 67-80. 130. Ishida, N., et al., Periodontitis induced by bacterial infection exacerbates features of Alzheimer's disease in transgenic mice. NPJ Aging Mech Dis, 2017. 3: p. 15. 131. Hajishengallis, G., R.P. Darveau, and M.A. Curtis, The keystone-pathogen hypothesis. Nat Rev Microbiol, 2012. 10(10): p. 717-25. 132. Sparks Stein, P., et al., Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease. Alzheimer's Dementia, 2012. 8(3): p. 196-203. 133. Kamer, A.R., et al., Periodontal disease as a possible cause for Alzheimer's disease. Periodontol 2000, 2020. 83(1): p. 242-271. 134. Blevins, S.M. and M.S. Bronze, Robert Koch and the 'golden age' of bacteriology. Int J Infect Dis, 2010. 14(9): p. e744-51. 135. Woese, C.R. and G.E. Fox, Phylogenetic structure of the prokaryotic domain: The primary kingdoms. Proceedings of the National Academy of Sciences, 1977. 74(11): p. 5088. 136. Sanger, F., S. Nicklen, and A.R. Coulson, DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, 1977. 74(12): p. 5463. 137. Watson, J.D. and R.M. Cook-Deegan, Origins of the Human Genome Project. Faseb j, 1991. 5(1): p. 8-11. 138. Pereira, R., J. Oliveira, and M. Sousa, Bioinformatics and Computational Tools for Next-Generation Sequencing Analysis in Clinical Genetics. J Clin Med, 2020. 9(1). 139. Rang, F.J., W.P. Kloosterman, and J. de Ridder, From squiggle to basepair: computational approaches for improving nanopore sequencing read accuracy. Genome Biology, 2018. 19(1): p. 90. 140. Handelsman, J., et al., Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chem Biol, 1998. 5(10): p. R245-9. 141. Ide, M., et al., Periodontitis and Cognitive Decline in Alzheimer's Disease. PLoS One, 2016. 11(3): p. e0151081. 142. Loe, H., The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol, 1967. 38(6): p. Suppl:610-6. 143. Lim, Y., et al., The saliva microbiome profiles are minimally affected by collection method or DNA extraction protocols. Scientific Reports, 2017. 7(1): p. 8523. 144. Caporaso, J.G., et al., Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms. Isme j, 2012. 6(8): p. 1621-4. 145. Qiu, C., M. Kivipelto, and E. von Strauss, Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention. Dialogues Clin Neurosci, 2009. 11(2): p. 111-28. 146. Martande, S., et al., Periodontal Health Condition in Patients With Alzheimer's Disease. American journal of Alzheimer's disease and other dementias, 2014. 29: p. 498-502. 147. Ebersole, J.L., et al., Aging, inflammation, immunity and periodontal disease. Periodontol 2000, 2016. 72(1): p. 54-75. 148. Lee, J.C., et al., Diagnosis of Alzheimer’s disease utilizing amyloid and tau as fluid biomarkers. Experimental Molecular Medicine, 2019. 51(5): p. 1-10. 149. Lue, L.-F., A. Guerra, and D.G. Walker, Amyloid Beta and Tau as Alzheimer's Disease Blood Biomarkers: Promise From New Technologies. Neurology and therapy, 2017. 6(Suppl 1): p. 25-36. 150. Shekhar, S., et al., Estimation of Tau and Phosphorylated Tau181 in Serum of Alzheimer's Disease and Mild Cognitive Impairment Patients. PloS one, 2016. 11(7): p. e0159099-e0159099. 151. Karadag, F., et al., The value of C-reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease. Eur J Intern Med, 2008. 19(2): p. 104-8. 152. Duong, T., M. Nikolaeva, and P.J. Acton, C-reactive protein-like immunoreactivity in the neurofibrillary tangles of Alzheimer's disease. Brain Res, 1997. 749(1): p. 152-6. 153. Iwamoto, N., et al., Demonstration of CRP immunoreactivity in brains of Alzheimer's disease: immunohistochemical study using formic acid pretreatment of tissue sections. Neurosci Lett, 1994. 177(1-2): p. 23-6. 154. Ravaglia, G., et al., Blood inflammatory markers and risk of dementia: The Conselice Study of Brain Aging. Neurobiol Aging, 2007. 28(12): p. 1810-20. 155. Song, I.U., et al., Relationship between the hs-CRP as non-specific biomarker and Alzheimer's disease according to aging process. Int J Med Sci, 2015. 12(8): p. 613-7. 156. O'Bryant, S.E., et al., Decreased C-reactive protein levels in Alzheimer disease. Journal of geriatric psychiatry and neurology, 2010. 23(1): p. 49-53. 157. Xu, L., et al., [Serum anti-Pg IgG antibody titers in patients with aggressive periodontitis]. Beijing Da Xue Xue Bao Yi Xue Ban, 2009. 41(1): p. 52-5. 158. Noble, J.M., et al., Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease. PLOS ONE, 2014. 9(12): p. e114959. 159. Fortea, J., et al., Cerebrospinal fluid β-amyloid and phospho-tau biomarker interactions affecting brain structure in preclinical Alzheimer disease. Ann Neurol, 2014. 76(2): p. 223-30. 160. Alcolea, D., et al., Agreement of amyloid PET and CSF biomarkers for Alzheimer's disease on Lumipulse. Annals of Clinical and Translational Neurology, 2019. 6(9): p. 1815-1824. 161. Brosseron, F., et al., Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer's disease. Alzheimer's research therapy, 2018. 10(1): p. 25-25. 162. Nishimura, F., et al., Porphyromonas gingivalis infection is associated with elevated C-reactive protein in nonobese Japanese type 2 diabetic subjects. Diabetes Care, 2002. 25(10): p. 1888. 163. Miyashita, H., et al., Relationship between serum antibody titres to Porphyromonas gingivalis and hs-CRP levels as inflammatory markers of periodontitis. Arch Oral Biol, 2012. 57(6): p. 820-9. 164. Weijenberg, R.A.F., et al., Mind your teeth—The relationship between mastication and cognition. Gerodontology, 2019. 36(1): p. 2-7. 165. Lexomboon, D., et al., Chewing Ability and Tooth Loss: Association with Cognitive Impairment in an Elderly Population Study. Journal of the American Geriatrics Society, 2012. 60(10): p. 1951-1956. 166. Miquel, S., M. Aspiras, and J.E.L. Day, Does reduced mastication influence cognitive and systemic health during aging? Physiology Behavior, 2018. 188: p. 239-250. 167. Tegeler, C., et al., The inflammatory markers CRP, IL-6, and IL-10 are associated with cognitive function--data from the Berlin Aging Study II. Neurobiol Aging, 2016. 38: p. 112-117. 168. D'Anna, L., et al., Serum Interleukin-10 Levels Correlate with Cerebrospinal Fluid Amyloid Beta Deposition in Alzheimer Disease Patients. Neurodegenerative Diseases, 2017. 17(4-5): p. 227-234. 169. Gajer, P., et al., Temporal dynamics of the human vaginal microbiota. Sci Transl Med, 2012. 4(132): p. 132ra52. 170. Hickey, R.J., et al., Vaginal microbiota of adolescent girls prior to the onset of menarche resemble those of reproductive-age women. mBio, 2015. 6(2). 171. Lee, J.E., et al., Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort. PLoS One, 2013. 8(5): p. e63514. 172. Srinivasan, S., et al., Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One, 2012. 7(6): p. e37818. 173. Zozaya, M., et al., Bacterial communities in penile skin, male urethra, and vaginas of heterosexual couples with and without bacterial vaginosis. Microbiome, 2016. 4: p. 16. 174. Smith, B.C., et al., The cervical microbiome over 7 years and a comparison of methodologies for its characterization. PLoS One, 2012. 7(7): p. e40425. 175. Greisen, K., et al., PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid. J Clin Microbiol, 1994. 32(2): p. 335-51. 176. Jo, J.H., E.A. Kennedy, and H.H. Kong, Research Techniques Made Simple: Bacterial 16S Ribosomal RNA Gene Sequencing in Cutaneous Research. J Invest Dermatol, 2016. 136(3): p. e23-e27. 177. Winand, R., et al., TARGETING THE 16S RRNA GENE FOR BACTERIAL IDENTIFICATION IN COMPLEX MIXED SAMPLES: COMPARATIVE EVALUATION OF SECOND (ILLUMINA) AND THIRD (OXFORD NANOPORE TECHNOLOGIES) GENERATION SEQUENCING TECHNOLOGIES. Int J Mol Sci, 2019. 21(1). 178. Bukin, Y.S., et al., The effect of 16S rRNA region choice on bacterial community metabarcoding results. Scientific Data, 2019. 6(1): p. 190007. 179. Teng, F., et al., Impact of DNA extraction method and targeted 16S-rRNA hypervariable region on oral microbiota profiling. Scientific Reports, 2018. 8(1): p. 16321. 180. Zheng, W., et al., An accurate and efficient experimental approach for characterization of the complex oral microbiota. Microbiome, 2015. 3: p. 48. 181. Rüdiger, S.G., et al., Dental biofilms at healthy and inflamed gingival margins. J Clin Periodontol, 2002. 29(6): p. 524-30. 182. Joshi, V., et al., Smoking decreases structural and functional resilience in the subgingival ecosystem. J Clin Periodontol, 2014. 41(11): p. 1037-47. 183. Haffajee, A.D., et al., Subgingival microbiota of chronic periodontitis subjects from different geographic locations. J Clin Periodontol, 2004. 31(11): p. 996-1002. 184. Willis, J.R., et al., Citizen science charts two major “stomatotypes” in the oral microbiome of adolescents and reveals links with habits and drinking water composition. Microbiome, 2018. 6(1): p. 218. 185. Caporaso, J.G., et al., Moving pictures of the human microbiome. Genome biology, 2011. 12(5): p. R50-R50. 186. Yatsunenko, T., et al., Human gut microbiome viewed across age and geography. Nature, 2012. 486(7402): p. 222-227. 187. Dioguardi, M., et al., The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer's Disease: A Systematic Review. Journal of clinical medicine, 2020. 9(2): p. 495. 188. Feres, M., et al., The subgingival periodontal microbiota of the aging mouth. Periodontology 2000, 2016. 72(1): p. 30-53. 189. Liu, X.X., et al., Analysis of Salivary Microbiome in Patients with Alzheimer's Disease. J Alzheimers Dis, 2019. 72(2): p. 633-640. 190. Cockburn, A.F., et al., High throughput DNA sequencing to detect differences in the subgingival plaque microbiome in elderly subjects with and without dementia. Investig Genet, 2012. 3(1): p. 19. 191. Nagy, E., Anaerobic Infections. Drugs, 2010. 70(7): p. 841-858. 192. Mohammedi, I., et al., Prevotella buccae bacteraemia associated with infection of a pseudoaneurysm. Eur J Vasc Endovasc Surg, 1998. 15(2): p. 175-6. 193. Cobo, F., et al., Infected breast cyst due to Prevotella buccae resistant to metronidazole. Anaerobe, 2017. 48: p. 177-178. 194. Duployez, C., et al., A case of bacteriemic mediastinitis due to Prevotella buccae after cardiac surgery. Anaerobe, 2020. 61: p. 102097. 195. Shen, L., L. Liu, and H.-F. Ji, Alzheimer’s Disease Histological and nbsp;Behavioral Manifestations in nbsp;Transgenic Mice Correlate with nbsp;Specific nbsp;Gut Microbiome State. Journal of Alzheimer's Disease, 2017. 56: p. 385-390. 196. Ciantar, M., et al., Capnocytophaga granulosa and Capnocytophaga haemolytica: novel species in subgingival plaque. J Clin Periodontol, 2001. 28(7): p. 701-5. 197. Pietiäinen, M., et al., Aggregatibacter actinomycetemcomitans serotypes associate with periodontal and coronary artery disease status. J Clin Periodontol, 2018. 45(4): p. 413-421. 198. Kobayashi, Y., et al., Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease. Sci Rep, 2017. 7(1): p. 13510. 199. Kaur, R., et al., Salivary levels of Bifidobacteria in caries-free and caries-active children. Int J Paediatr Dent, 2013. 23(1): p. 32-8. 200. Hojo, K., et al., Distribution of Salivary Lactobacillus and Bifidobacterium Species in Periodontal Health and Disease. Bioscience, Biotechnology, and Biochemistry, 2007. 71(1): p. 152-157. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78344 | - |
| dc.description.abstract | 研究背景：阿茲海默症是一種神經退化性疾病，致病機轉被認為和中樞以及周邊發炎反應有關係。牙周病亦是一種與發炎高度相關的疾病，流行病學研究指出牙周病患者有較高的風險發展成阿茲海默症，但牙周病如何影響阿茲海默症的機轉尚未釐清。本研究藉由觀察阿茲海默症患者與對照者(非阿茲海默症患者)之臨床牙周健康狀況、血清相關發炎因子濃度、唾液細菌種類分布，以比較阿茲海默症患者的失智嚴重度(CDR)、血清標記因子、口腔菌系組成與牙周病嚴重程度之間的關係，以探討阿茲海默症及牙周病之間的相關性。 材料與方法：共31名輕度至中度之單純阿茲海默型失智患者(AD)與31名健康對照組(Control)納入本實驗，進行問卷填寫以調查人口學資料、個人習慣、過去病史、家族病史、牙科照護習慣，並且進行全口牙周檢查（殘留齒數、牙周囊袋深度、臨床附連喪失、牙菌斑指數、牙齦發炎指數、放射線骨高度），並檢測血清中A42、pTau、Tau、IL-10、TNF-α、IL-1β、IL-6、IL-8、hsCRP、anti-P. gingivalis LPS抗體的濃度。亦收集受試者的唾液進行DNA萃取、16S rDNA (V3-V4) 次世代基因定序(Illumina®)以分析口腔微生物菌系組成。 結果：1. 首先以年齡-性別配對方法篩選後得到兩組各20名受試者：AD組的血清標記因子Tau、hsCRP、Anti-P. gingivalis LPS抗體濃度顯著高於Control組，Anti-P. gingivalis LPS抗體和hsCRP之濃度呈顯著正相關，和IL-10之濃度呈顯著負相關；hsCRP之濃度則和A42、Tau、pTau之濃度呈顯著正相關，和IL-10之濃度、後牙植牙數量呈顯著負相關。此外，AD組的教育程度顯著低於Control組、口腔衛生照護習慣亦顯著不足，但並未發現AD組之牙周疾病嚴重度、缺牙情況、系統性疾病複雜程度相較Control組嚴重。2. 其次，比較所有收案AD組(n=31)：臨床附連喪失小於4釐米(CAL<4mm) 和CDR分數之間為顯著負相關，血清中的A42濃度和Tau、pTau、hsCRP、IL-1濃度呈正相關。3. 最後比較所有收案之AD組(n=31)和Control組(n=31)之口腔微生物菌系差異：兩組間並無物種豐度和分佈比例上的顯著差異，唯有5~6%的物種組成差異，若以菌屬劃分發現Prevotella、Peptococcus 、Faecalibacterium、Anoxybacillus在AD族群中顯著較多，若以菌種劃分則發現Prevotella buccae 在AD組中顯著較多。 結論：本研究發現失智越嚴重，臨床牙周附連喪失程度越多。AD組的血清hsCRP濃度顯著較高，與AD成因相關之Tau蛋白濃度亦較高，顯示慢性發炎和AD的正關聯性，且Anti-P. gingivalis LPS抗體和hsCRP濃度呈正相關，提供牙周病和系統性慢性發炎的相關性。但AD組和Control組的牙周病嚴重度和口腔微生物菌系組成不具顯著差異。雖發現AD族群口腔微生物菌系中有極少量細菌比例顯著較多，但這些細菌對於AD可能造成的影響仍須後續更多的研究探討。 | zh_TW |
| dc.description.abstract | Objectives: Alzheimer disease (AD) is a neurodegenerative disease associating with central and peripheral inflammatory responses. Periodontal disease is a bacteria-induced chronic inflammatory disease. Epidemiological studies have reported that patients with periodontal disease have a higher risk of developing AD, but the mechanism was not yet been fully understood. The aim of this study was to explore the association between AD and periodontal diseases in a case-control study. Methods: 31 patients with slight or moderate AD (no mixed type dementia) and 31 controls without AD were enrolled in this study. Each participant or the main care giver was asked to fill the questionnaire about the individual’s family history of dementia, family history of periodontal disease, present and past medication history. In addition, past dental maintenance frequency, daily oral hygiene care and personal habit such as smoking were recorded. All the participants received periodontal charting and radiographic film to record periodontal parameters, the number of remaining teeth and the bone level of bilateral mandibular posterior teeth. In addition, the blood was collected to detect serum biomarker including A42, Tau, pTau, pro-inflammatory cytokines, anti-P. gingivalis LPS antibodies, and triglyceride. The saliva samples were also collected for analyzing the oral miciobiota by 16S rDNA (V3-V4) NGS technique. Results: After the age and gender matching (AD/control = 20/20), the AD patients showed lower education level, and higher serum concentration of Tau、hsCRP、anti-P. gingivalis LPS antibody with significancy. In addition, serum anti-P. gingivalis LPS antibody was positively correlated to serum hsCRP, but negatively correlated to serum IL-10. Also, serum hsCRP was positively correlated to serum A42, Tau and pTau; but negatively correlated to serum IL-10 and number of posterior dental implants. However, there was no significant difference between groups in the severity of periodontal disease and the complexicity of systemic medical history. As for intra-group analysis of all AD participants (n=31), CDR score was negatively correlated to clinical attachment loss (CAL)<4mm with significancy. Besides, serum concentration of A42 was positively correlated to Tau、pTau、hsCRP、IL-1. Finally, the main composition of the oral microbiota was similar with only 5~6% difference in bacteria diversity between two groups (AD/control = 31/31). Four bacteria genus (Prevotella, Peptococcus, Faecalibacterium, Anoxybacillus) and 1 bacteria species (Prevotella buccae) were signigicantly associated with AD. Conclusions: With the limitation of this study, we conclude that AD was associated with higher serum hsCRP, Tau protein, and anti-P. gingivalis LPS antibod. However, the periodontal condition of in AD group was not significantly severer then the control. Within the AD patients, the severity of the dementia was positively correlated to the amount of periodontal clinical attachment loss. Even though very few bacteria abundance of oral micriobiota was significantly higher in the AD group, the majority of the composition was similar in the two groups. Further studies are warranted to varify the role of these bacteria in the pathogenesis of AD. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:52:13Z (GMT). No. of bitstreams: 1 U0001-3007202011141200.pdf: 10977000 bytes, checksum: 5655f0a3d106b415dd75934d1518b452 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 誌謝 3 中文摘要 4 Abstract 5 圖目錄 9 表目錄 11 第一章、緒論 12 第一節、阿茲海默症失智症(Alzheimer’s Disease) 12 1-1、流行病學 12 1-2、AD的成因 13 1-3、AD的臨床表現和診斷 17 1-4、AD和微生物群系(Microbiome)的關聯性 19 1-5、AD和發炎因子 21 1-6、AD的共病症、風險因子、保護因子 25 1-7、AD的治療方式 29 第二節、牙周病(Periodontitis) 31 2-1、流行病學 31 2-2、牙周病的成因 32 2-3、牙周病的臨床表現和診斷 36 2-4、牙周病和微生物菌叢的關係 39 2-5、牙周病和發炎因子的關係 42 2-6、牙周病的危險因子 43 2-7、牙周病的治療 44 第三節、AD和牙周病之間的關係 46 第四節、利用次世代基因定序技術研究微生物菌系 49 4-1、微生物菌叢研究方法的沿革 49 4-2、16S核糖體RNA基因(16S ribosomal RNA gene) 52 4-3、生物多樣性 53 第二章、實驗目的 55 第三章、實驗材料與方法 56 第一節、受試者招募 56 1-1、基本條件 56 1-2. 病例組的選擇(Case group : AD group) 56 1-3. 對照組的選擇(Control group) 56 第二節、問卷調查 57 第三節、臨床牙周檢查及口腔放射線檢查 59 第四節、血液收集及檢驗 59 4-1、血液收集 59 4-2、酵素免疫分析法(Enzyme-linked immunosorbent assay, ELISA) 60 4-3、三酸甘油脂(Triglyceride; TG)試片檢查 65 第五節、唾液收集及檢測 66 5-1、唾液收集及保存 66 5-2、DNA 萃取(DNA Extraction) 66 5-3、PCR 68 5-4、NGS 69 實驗流程圖 70 第六節、統計方法 71 6-1、Mann-Whitney U Test 71 6-2、Pearson’s chi-square test 71 6-3、Spearman’s rank-order correlation 72 6-4、唾液樣本進行NGS後的結果(微生物菌系分析)： 72 第四章、結果 74 第一節、病例組(Case: AD)及對照組(Control: non-AD)組之收案特色 74 第二節、病例組及對照組之牙周健康狀況分析 76 第三節、病例組及對照組之血清生物標記因子(Biomarker)分析 77 第四節、AD與探討因子之間的相關性(correlation) 81 4-1、性別-年齡對照(Age-gender matched)下的案例(n=40)之多因子比較 81 4-2、全部收案之Case組(n=31)之AD嚴重程度與探討因子之間的關聯性 84 第五節、病例組及對照組之唾液微生物菌系(Microbiota)經NGS法之分析 87 第五章、討論 115 第一節、探討病例組及對照組之牙周及血清檢查結果 115 第二節、多因子相關性分析 118 第三節、微生物菌系之組成比例無顯著差異 120 第四節、未來研究方向(Future work) 125 第六章、結論 126 參考文獻 127 | |
| dc.language.iso | zh-TW | |
| dc.subject | 次世代基因定序 | zh_TW |
| dc.subject | 牙周病 | zh_TW |
| dc.subject | 阿滋海默症 | zh_TW |
| dc.subject | 口腔微生物菌系 | zh_TW |
| dc.subject | 血清牙齦卟啉單胞菌抗體 | zh_TW |
| dc.subject | 16S 核糖體RNA基因 | zh_TW |
| dc.subject | 16S rDNA | en |
| dc.subject | Periodontitis | en |
| dc.subject | Alzheimer's disease | en |
| dc.subject | Oral Microbiota | en |
| dc.subject | Anti porphyromonas gingivalis LPS antibody | en |
| dc.subject | Next Generation Sequencing | en |
| dc.title | 從血清學和口腔微生物群之角度研究阿滋海默症與牙周病之間的關連：病例對照研究 | zh_TW |
| dc.title | The Associations between Alzheimer’s disease and periodontitis from the aspects of serology and oral-microbiota: A Case-control study | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 侯欣翰(Hsin-Han Hou),洪千岱(Chien-Tai Hong) | |
| dc.subject.keyword | 牙周病,阿滋海默症,口腔微生物菌系,血清牙齦卟啉單胞菌抗體,16S 核糖體RNA基因,次世代基因定序, | zh_TW |
| dc.subject.keyword | Periodontitis,Alzheimer's disease,Oral Microbiota,Anti porphyromonas gingivalis LPS antibody,16S rDNA,Next Generation Sequencing, | en |
| dc.relation.page | 141 | |
| dc.identifier.doi | 10.6342/NTU202002081 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-07 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2025-08-01 | - |
| 顯示於系所單位： | 臨床牙醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-3007202011141200.pdf 未授權公開取用 | 10.72 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。