Display options
Cite
Sun Q, Xie N, Tang B, et al. Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms. Front Mol Neurosci. 2017;10:319doi: 10.3389/fnmol.2017.00319.
Sun, Q., Xie, N., Tang, B., Li, R., & Shen, Y. (2017). Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms. Frontiers in molecular neuroscience, 10319. https://doi.org/10.3389/fnmol.2017.00319
Sun, Qiying, et al. "Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms." Frontiers in molecular neuroscience vol. 10 (2017): 319. doi: https://doi.org/10.3389/fnmol.2017.00319
Sun Q, Xie N, Tang B, Li R, Shen Y. Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms. Front Mol Neurosci. 2017 Oct 06;10:319. doi: 10.3389/fnmol.2017.00319. eCollection 2017. PMID: 29056900; PMCID: PMC5635057.
Copy Download .nbib Format: NLM
Share it on

Front Mol Neurosci. 2017 Oct 06;10:319. doi: 10.3389/fnmol.2017.00319. eCollection 2017.

Alzheimer's Disease: From Genetic Variants to the Distinct Pathological Mechanisms.

Frontiers in molecular neuroscience

Qiying Sun, Nina Xie, Beisha Tang, Rena Li, Yong Shen

Affiliations

  1. Department of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha, China.
  2. Center for Advanced Therapeutic Strategies for Brain Disorders and Center for Hormone Advanced Science and Education, Roskamp Institute, Sarasota, FL, United States.
  3. National Clinical Research Center for Mental Disorders, Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.
  4. Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.
  5. Neurodegenerative Disorder Research Center, University of Science and Technology of China School of Life Sciences, Hefei, China.
  6. Hefei Material Science at Microscale National Laboratory, Hefei, China.

PMID: 29056900 PMCID: PMC5635057 DOI: 10.3389/fnmol.2017.00319

Abstract

Being the most common cause of dementia, AD is a polygenic and neurodegenerative disease. Complex and multiple factors have been shown to be involved in its pathogenesis, of which the genetics play an indispensable role. It is widely accepted that discovery of potential genes related to the pathogenesis of AD would be of great help for the understanding of neurodegeneration and thus further promote molecular diagnosis in clinic settings. Generally, AD could be clarified into two types according to the onset age, the early-onset AD (EOAD) and the late-onset AD (LOAD). Progresses made by genetic studies on both EOAD and LOAD are believed to be essential not only for the revolution of conventional ideas but also for the revelation of new pathological mechanisms underlying AD pathogenesis. Currently, albeit the genetics of LOAD is much less well-understood compared to EOAD due to its complicated and multifactorial essence, Genome-wide association studies (GWASs) and next generation sequencing (NGS) approaches have identified dozens of novel genes that may provide insight mechanism of LOAD. In this review, we analyze functions of the genes and summarize the distinct pathological mechanisms of how these genes would be involved in the pathogenesis of AD.

Keywords: Alzheimer’s disease; EOAD; GWASs; LOAD; genetics; mechanism

References

  1. Nat Genet. 2011 May;43(5):436-41 - PubMed
  2. Biochem Soc Trans. 2015 Oct;43(5):920-3 - PubMed
  3. Neurology. 2002 May 28;58(10):1574-5 - PubMed
  4. Curr Atheroscler Rep. 2013 Mar;15(3):307 - PubMed
  5. Lancet Neurol. 2015 Apr;14(4):388-405 - PubMed
  6. Blood. 2009 Mar 26;113(13):2924-33 - PubMed
  7. Science. 2011 Dec 2;334(6060):1241-5 - PubMed
  8. Curr Opin Neurobiol. 2016 Feb;36:74-81 - PubMed
  9. Immunobiology. 2012 Feb;217(2):244-50 - PubMed
  10. Nature. 2011 Aug 10;476(7359):214-9 - PubMed
  11. Nat Rev Neurosci. 2008 Dec;9(12):899-909 - PubMed
  12. Cell. 2003 Apr 4;113(1):37-47 - PubMed
  13. Cell Res. 2010 Jan;20(1):34-50 - PubMed
  14. Nat Rev Mol Cell Biol. 2002 Jul;3(7):475-86 - PubMed
  15. Neuroepidemiology. 1999;18(1):48-52 - PubMed
  16. Alzheimers Dement. 2015 Mar;11(3):332-84 - PubMed
  17. Arch Neurol. 2004 Aug;61(8):1200-5 - PubMed
  18. Nat Rev Neurol. 2011 Mar;7(3):137-52 - PubMed
  19. Biochim Biophys Acta. 2010 Aug;1801(8):762-73 - PubMed
  20. J Comp Neurol. 2005 Jan 3;481(1):58-69 - PubMed
  21. Nature. 1995 Jun 29;375(6534):754-60 - PubMed
  22. Biol Psychiatry. 2015 Jan 1;77(1):43-51 - PubMed
  23. Acta Neuropathol. 2013 Jun;125(6):861-78 - PubMed
  24. N Engl J Med. 2013 Jan 10;368(2):107-16 - PubMed
  25. Alzheimers Dement. 2013 Sep;9(5):546-53 - PubMed
  26. Ann N Y Acad Sci. 2008 Nov;1143:61-82 - PubMed
  27. Ageing Res Rev. 2012 Jan;11(1):87-103 - PubMed
  28. Neurobiol Aging. 2012 Jan;33(1):210.e1-7 - PubMed
  29. N Engl J Med. 2013 Jan 10;368(2):117-27 - PubMed
  30. Proc Natl Acad Sci U S A. 1996 May 14;93(10):4804-9 - PubMed
  31. Annu Rev Neurosci. 2011;34:185-204 - PubMed
  32. Mol Brain. 2011 Jan 07;4:3 - PubMed
  33. Neuroscience. 2015 Aug 27;302:138-50 - PubMed
  34. Am J Pathol. 2001 Dec;159(6):2303-8 - PubMed
  35. Nat Neurosci. 2013 Jul;16(7):848-50 - PubMed
  36. Lancet. 2003 Nov 22;362(9397):1746-8 - PubMed
  37. Neuron. 1990 Dec;5(6):831-9 - PubMed
  38. Cell. 2013 Oct 10;155(2):435-47 - PubMed
  39. EMBO Rep. 2014 Oct;15(10):1036-52 - PubMed
  40. Neurology. 2012 Jul 17;79(3):221-8 - PubMed
  41. Neurol Neurochir Pol. 2013 Mar-Apr;47(2):157-60 - PubMed
  42. Biochem Biophys Res Commun. 1994 Nov 15;204(3):1131-6 - PubMed
  43. Clin Interv Aging. 2014 Apr 01;9:535-51 - PubMed
  44. Neurobiol Aging. 2014 Feb;35(2):279-90 - PubMed
  45. Nat Genet. 1992 Aug;1(5):345-7 - PubMed
  46. Science. 1990 Jun 1;248(4959):1124-6 - PubMed
  47. Hum Mol Genet. 2000 Nov 1;9(18):2589-98 - PubMed
  48. Exp Hematol. 2003 Dec;31(12 ):1170-81 - PubMed
  49. J Alzheimers Dis. 2011;25(1):111-7 - PubMed
  50. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13221-6 - PubMed
  51. Eur J Biochem. 1994 May 1;221(3):917-25 - PubMed
  52. Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13461-6 - PubMed
  53. PLoS One. 2012;7(2):e31039 - PubMed
  54. Sci Transl Med. 2011 Jun 29;3(89):89ra57 - PubMed
  55. Nature. 1991 Feb 21;349(6311):704-6 - PubMed
  56. J Neurosci. 2014 Sep 3;34(36):11929-47 - PubMed
  57. Nat Genet. 2009 Oct;41(10):1088-93 - PubMed
  58. Hum Mol Genet. 2009 Oct 15;18(20):3987-96 - PubMed
  59. Cell. 1998 Sep 4;94(5):667-77 - PubMed
  60. Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17071-6 - PubMed
  61. Ann Hum Genet. 2012 Nov;76(6):448-53 - PubMed
  62. Acta Neuropathol. 2010 Dec;120(6):803-12 - PubMed
  63. Gut. 2012 Jun;61(6):956-7 - PubMed
  64. Cell. 2012 Mar 16;148(6):1204-22 - PubMed
  65. Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1807-16 - PubMed
  66. Neuropharmacology. 2014 Jan;76 Pt A:27-50 - PubMed
  67. Annu Rev Genomics Hum Genet. 2000;1:507-37 - PubMed
  68. Neurology. 2000 Jan 11;54(1):240-2 - PubMed
  69. J Neurochem. 2008 Mar;104(5):1145-66 - PubMed
  70. Curr Opin Neurobiol. 2009 Jun;19(3):275-83 - PubMed
  71. Trends Mol Med. 2013 Oct;19(10):594-603 - PubMed
  72. Neurobiol Dis. 2014 Dec;72 Pt A:3-12 - PubMed
  73. PLoS One. 2012;7(11):e50976 - PubMed
  74. Nat Rev Neurol. 2013 Apr;9(4):184 - PubMed
  75. Int J Cell Biol. 2013;2013:576383 - PubMed
  76. PLoS Genet. 2012;8(11):e1003067 - PubMed
  77. Neurobiol Aging. 2009 Jul;30(7):1048-51 - PubMed
  78. J Mol Med (Berl). 2014 May;92(5):453-63 - PubMed
  79. Nat Genet. 2011 May;43(5):429-35 - PubMed
  80. Arch Immunol Ther Exp (Warsz). 2015 Oct;63(5):333-44 - PubMed
  81. Nat Genet. 2009 Oct;41(10):1094-9 - PubMed
  82. Science. 2009 Mar 13;323(5920):1473-7 - PubMed
  83. Science. 1987 Feb 20;235(4791):877-80 - PubMed
  84. Biomed Res Int. 2014;2014:291862 - PubMed
  85. Am J Hum Genet. 1992 Nov;51(5):998-1014 - PubMed
  86. Oxid Med Cell Longev. 2013;2013:860959 - PubMed
  87. J Cereb Blood Flow Metab. 2007 May;27(5):909-18 - PubMed
  88. Clin Chem. 1995 Aug;41(8 Pt 1):1068-86 - PubMed
  89. Microsc Res Tech. 2000 Aug 15;50(4):305-15 - PubMed
  90. Neurology. 1999 Feb;52(3):551-6 - PubMed
  91. Annu Rev Genomics Hum Genet. 2013;14:301-23 - PubMed
  92. J Biol Chem. 2005 Feb 4;280(5):3989-95 - PubMed
  93. Nature. 2014 Jan 23;505(7484):550-554 - PubMed
  94. J Atheroscler Thromb. 2011;18(4):274-81 - PubMed
  95. J Biol Chem. 2008 Oct 31;283(44):29627-31 - PubMed
  96. Hum Mutat. 2008 May;29(5):769-70 - PubMed
  97. Nat Genet. 2013 Dec;45(12):1452-8 - PubMed
  98. J Neurol. 2003 Nov;250(11):1374-5 - PubMed
  99. Front Biosci. 2007 May 01;12 :2836-48 - PubMed
  100. Immunobiology. 2012 Feb;217(2):204-15 - PubMed
  101. Hum Mol Genet. 2014 Nov 1;23(21):5838-46 - PubMed
  102. Eur J Cell Biol. 2009 Feb;88(2):91-102 - PubMed
  103. Nat Genet. 1996 Sep;14(1):69-77 - PubMed
  104. EMBO J. 1998 Apr 1;17 (7):1961-72 - PubMed
  105. Neurobiol Dis. 2003 Dec;14(3):619-23 - PubMed
  106. Hum Mol Genet. 2014 Feb 15;23(4):870-7 - PubMed
  107. Biochim Biophys Acta. 2010 Aug;1801(8):754-61 - PubMed
  108. Mol Biol Cell. 1999 Aug;10(8):2687-702 - PubMed
  109. Nat Rev Immunol. 2003 Jun;3(6):445-53 - PubMed
  110. JAMA. 2010 May 12;303(18):1832-40 - PubMed
  111. Nat Genet. 1992 Jun;1(3):218-21 - PubMed
  112. Lancet. 2011 Feb 19;377(9766):641-9 - PubMed
  113. JAMA Neurol. 2015 Jan;72(1):15-24 - PubMed
  114. FASEB J. 2007 Aug;21(10):2312-22 - PubMed
  115. Gene. 2017 Jan 15;597:10-16 - PubMed
  116. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3922-7 - PubMed
  117. Neurology. 2005 May 10;64(9):1502-7 - PubMed
  118. Neurology. 2008 Mar 11;70(11):887-9 - PubMed
  119. Am J Hum Genet. 2003 Jul;73(1):174-87 - PubMed
  120. Neurobiol Aging. 1996 Sep-Oct;17(5):707-16 - PubMed
  121. Mol Immunol. 2008 Mar;45(5):1208-20 - PubMed
  122. Arch Med Res. 2012 Nov;43(8):622-31 - PubMed
  123. Brain. 2010 Apr;133(Pt 4):1155-62 - PubMed
  124. Brain Res Rev. 2009 Oct;61(2):89-104 - PubMed
  125. Arch Med Res. 2012 Nov;43(8):595-9 - PubMed
  126. Arch Neurol. 2010 Jun;67(6):677-85 - PubMed
  127. Neurobiol Aging. 2012 Sep;33(9):2231.e15-2231.e30 - PubMed
  128. Neuron. 2007 Aug 16;55(4):565-71 - PubMed
  129. Nat Rev Neurol. 2013 Feb;9(2):106-18 - PubMed
  130. Nature. 1995 Aug 31;376(6543):775-8 - PubMed
  131. Mol Immunol. 2010 Feb;47(5):1074-82 - PubMed
  132. Acta Neurobiol Exp (Wars). 2009;69(2):232-53 - PubMed
  133. J Neurosci. 2013 Aug 14;33(33):13320-5 - PubMed
  134. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4119-24 - PubMed
  135. Hum Mol Genet. 1997 Nov;6(12):2087-9 - PubMed
  136. Prog Mol Biol Transl Sci. 2012;107:263-93 - PubMed
  137. Ann Neurol. 2001 Jun;49(6):697-705 - PubMed
  138. Biochem Pharmacol. 2014 Apr 15;88(4):495-8 - PubMed
  139. Neurosci Lett. 2009 Sep 18;461(2):177-80 - PubMed
  140. J Neurosci. 2006 Feb 1;26(5):1596-603 - PubMed
  141. J Neurochem. 2001 Mar;76(5):1532-9 - PubMed
  142. Prog Neurobiol. 2015 Dec;135:1-20 - PubMed
  143. Alzheimers Dement. 2014 Nov;10(6):861-8 - PubMed
  144. Neuroreport. 2006 Jun 26;17(9):891-6 - PubMed
  145. Science. 1995 Aug 18;269(5226):973-7 - PubMed

Publication Types

Grant support