Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States

Author:

Wang Li-San1,Naj Adam C.2,Graham Robert R.3,Crane Paul K.4,Kunkle Brian W.5,Cruchaga Carlos6,Murcia Josue D. Gonzalez7,Cannon-Albright Lisa8,Baldwin Clinton T.9,Zetterberg Henrik10,Blennow Kaj11,Kukull Walter A.12,Faber Kelley M.13,Schupf Nicole14,Norton Maria C.15,Tschanz JoAnn T.16,Munger Ronald G.17,Corcoran Christopher D.18,Rogaeva Ekaterina19,Lin Chiao-Feng1,Dombroski Beth A.1,Cantwell Laura B.1,Partch Amanda1,Valladares Otto1,Hakonarson Hakon20,St George-Hyslop Peter21,Green Robert C.22,Goate Alison M.6,Foroud Tatiana M.13,Carney Regina M.23,Larson Eric B.24,Behrens Timothy W.3,Kauwe John S. K.7,Haines Jonathan L.25,Farrer Lindsay A.26,Pericak-Vance Margaret A.27,Mayeux Richard28,Schellenberg Gerard D.1,Albert Marilyn S.29,Albin Roger L.30,Apostolova Liana G.31,Arnold Steven E.32,Barber Robert33,Barmada M. Michael34,Barnes Lisa L.35,Beach Thomas G.36,Becker James T.37,Beecham Gary W.38,Beekly Duane39,Bennett David A.40,Bigio Eileen H.41,Bird Thomas D.42,Blacker Deborah43,Boeve Bradley F.44,Bowen James D.45,Boxer Adam46,Burke James R.47,Buxbaum Joseph D.48,Cairns Nigel J.49,Cao Chuanhai50,Carlson Chris S.51,Carroll Steven L.52,Chui Helena C.53,Clark David G.54,Cribbs David H.55,Crocco Elizabeth A.23,DeCarli Charles56,DeKosky Steven T.57,Demirci F. Yesim34,Dick Malcolm58,Dickson Dennis W.59,Duara Ranjan60,Ertekin-Taner Nilufer61,Fallon Kenneth B.52,Farlow Martin R.62,Ferris Steven63,Frosch Matthew P.64,Galasko Douglas R.65,Ganguli Mary66,Gearing Marla67,Geschwind Daniel H.68,Ghetti Bernardino69,Gilbert John R.38,Glass Jonathan D.70,Graff-Radford Neill R.61,Growdon John H.71,Hamilton Ronald L.72,Hamilton-Nelson Kara L.5,Harrell Lindy E.54,Head Elizabeth73,Honig Lawrence S.74,Hulette Christine M.75,Hyman Bradley T.71,Jarvik Gail P.76,Jicha Gregory A.77,Jin Lee-Way78,Jun Gyungah79,Kamboh M. Ilyas80,Karydas Anna46,Kaye Jeffrey A.81,Kim Ronald82,Koo Edward H.65,Kowall Neil W.83,Kramer Joel H.84,Kramer Patricia85,LaFerla Frank M.86,Lah James J.70,Leverenz James B.87,Levey Allan I.70,Li Ge88,Lieberman Andrew P.89,Lopez Oscar L.90,Lunetta Kathryn L.91,Lyketsos Constantine G.92,Mack Wendy J.93,Marson Daniel C.54,Martin Eden R.38,Martiniuk Frank94,Mash Deborah C.95,Masliah Eliezer96,McCormick Wayne C.4,McCurry Susan M.97,McDavid Andrew N.51,McKee Ann C.83,Mesulam M. Marsel98,Miller Bruce L.46,Miller Carol A.99,Miller Joshua W.78,Montine Thomas J.87,Morris John C.100,Murrell Jill R.101,Olichney John M.56,Parisi Joseph E.102,Perry William5,Peskind Elaine88,Petersen Ronald C.44,Pierce Aimee55,Poon Wayne W.58,Potter Huntington50,Quinn Joseph F.103,Raj Ashok50,Raskind Murray88,Reiman Eric M.104,Reisberg Barry105,Reitz Christiane106,Ringman John M.31,Roberson Erik D.54,Rosen Howard J.46,Rosenberg Roger N.107,Sano Mary108,Saykin Andrew J.109,Schneider Julie A.110,Schneider Lon S.111,Seeley William W.46,Smith Amanda G.50,Sonnen Joshua A.87,Spina Salvatore69,Stern Robert A.112,Tanzi Rudolph E.71,Thornton-Wells Tricia A.25,Trojanowski John Q.1,Troncoso Juan C.113,Tsuang Debby W.114,Van Deerlin Vivianna M.1,Van Eldik Linda J.115,Vardarajan Badri N.106,Vinters Harry V.116,Vonsattel Jean Paul117,Weintraub Sandra118,Welsh-Bohmer Kathleen A.119,Williamson Jennifer120,Wishnek Sarah5,Woltjer Randall L.121,Wright Clinton B.122,Younkin Steven G.59,Yu Chang-En4,Yu Lei123

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia

2. Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia

3. Department of Human Genetics, Genentech Inc, South San Francisco, California

4. Department of Medicine, University of Washington, Seattle

5. John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida

6. Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri7Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, Missouri

7. Department of Biology, Brigham Young University, Provo, Utah

8. Division of Genetic Epidemiology, Department of Medicine, University of Utah School of Medicine, Salt Lake City10George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah

9. Biomedical Genetics, Department of Medicine, Boston University, Boston, Massachusetts

10. Institute of Neurology, University College London, London, England13Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska Uni

11. Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Mölndal, Sweden

12. Department of Epidemiology, University of Washington, Seattle

13. Department of Medical and Molecular Genetics, Indiana University, Indianapolis

14. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York17Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York18Gertrude H. Sergievsky Center, Columbia

15. Department of Family, Consumer, and Human Development, Utah State University, Logan20Department of Psychology, Utah State University, Logan

16. Department of Psychology, Utah State University, Logan

17. Department of Nutrition, Dietetics, and Food Sciences, Utah State University, Logan

18. Department of Mathematics and Statistics, Utah State University, Logan

19. Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada

20. Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

21. Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Ontario, Canada25Cambridge Institute for Medical Research, Department of Clinical Neurosciences, University of Cambridge, Cambridge, England

22. Division of Genetics, Department of Medicine and Partners Center for Personalized Genetic Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts

23. Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, Florida

24. Department of Medicine, University of Washington, Seattle28Group Health Research Institute, Seattle, Washington

25. Center for Human Genetics and Research, Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee

26. Department of Biology, Brigham Young University, Provo, Utah30Department of Biostatistics, Boston University, Boston, Massachusetts31Department of Ophthalmology, Boston University, Boston, Massachusetts32Department of Neurology, Boston University, Boston,

27. John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida34Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida

28. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York18Gertrude H. Sergievsky Center, Columbia University, New York, New York35Department of Neurology, Columbia University, New York, New York

29. Department of Neurology, Johns Hopkins University, Baltimore, Maryland

30. Department of Neurology, University of Michigan, Ann Arbor38Geriatric Research, Education, and Clinical Center, VA Ann Arbor Healthcare System, Ann Arbor, Michigan39Michigan Alzheimer’s Disease Center, Ann Arbor

31. Department of Neurology, University of California, Los Angeles

32. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia

33. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth

34. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania

35. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois45Department of Behavioral Sciences, Rush University Medical Center, Chicago, Illinois

36. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Phoenix, Arizona

37. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania48Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania49Department of Psychology, University of Pittsburgh School of M

38. John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida51Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida

39. National Alzheimer’s Coordinating Center, University of Washington, Seattle

40. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois53Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois

41. Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois55Cognitive Neurology and Alzheimer’s Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois

42. Geriatric Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, Washington57Department of Neurology, University of Washington, Seattle

43. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts59Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston

44. Department of Neurology, Mayo Clinic, Rochester, Minnesota

45. Swedish Medical Center, Seattle, Washington

46. Department of Neurology, University of California, San Francisco

47. Department of Medicine, Duke University, Durham, North Carolina

48. Department of Neuroscience, Mount Sinai School of Medicine, New York, New York65Department of Psychiatry, Mount Sinai School of Medicine, New York, New York66Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York

49. Department of Pathology and Immunology, Washington University, St Louis, Missouri

50. USF Health Byrd Alzheimer’s Institute, University of South Florida, Tampa

51. Fred Hutchinson Cancer Research Center, Seattle, Washington

52. Department of Pathology, University of Alabama at Birmingham, Birmingham

53. Department of Neurology, University of Southern California, Los Angeles

54. Department of Neurology, University of Alabama at Birmingham, Birmingham

55. Department of Neurology, University of California, Irvine

56. Department of Neurology, University of California, Davis, Sacramento

57. University of Virginia School of Medicine, Charlottesville77now with University of Pittsburgh, Pittsburgh, Pennsylvania

58. Institute for Memory Impairments and Neurological Disorders, University of California, Irvine

59. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida

60. Wien Center for Alzheimer’s Disease and Memory Disorders, Mount Sinai Medical Center, Miami Beach, Florida

61. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida81Department of Neurology, Mayo Clinic, Jacksonville, Florida

62. Department of Neurology, Indiana University, Indianapolis

63. Department of Psychiatry, New York University, New York

64. C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Charlestown

65. Department of Neurosciences, University of California, San Diego, La Jolla

66. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

67. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia87Alzheimer’s Disease Research Center, Emory University, Atlanta, Georgia

68. Neurogenetics Program, University of California, Los Angeles

69. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis

70. Department of Neurology, Emory University, Atlanta, Georgia

71. Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston

72. Division of Neuropathology, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania

73. Department of Molecular and Biomedical Pharmacology, Sanders-Brown Center on Aging, University of Kentucky, Lexington

74. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York95Department of Neurology, Columbia University, New York, New York

75. Department of Pathology, Duke University, Durham, North Carolina

76. Department of Genome Sciences, University of Washington, Seattle98Division of Medical Genetics, Department of Medicine, University of Washington, Seattle

77. Department of Neurology, Sanders-Brown Center on Aging, University of Kentucky, Lexington

78. Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento

79. Genetics Program, Department of Medicine, Boston University, Boston, Massachusetts102Department of Biostatistics, Boston University, Boston, Massachusetts103Department of Ophthalmology, Boston University, Boston, Massachusetts

80. Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania104Alzheimer Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania

81. Department of Neurology, Oregon Health & Science University, Portland106Department of Neurology, Portland Veterans Affairs Medical Center, Portland, Oregon

82. Department of Pathology and Laboratory Medicine, University of California, Irvine

83. Department of Neurology, Boston University, Boston, Massachusetts109Department of Pathology, Boston University, Boston, Massachusetts

84. Department of Neuropsychology, University of California, San Francisco

85. Department of Neurology, Oregon Health & Science University, Portland111Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland

86. Department of Neurobiology and Behavior, University of California, Irvine

87. Department of Pathology, University of Washington, Seattle

88. Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle

89. Department of Pathology, University of Michigan, Ann Arbor

90. Alzheimer Disease Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania

91. Department of Biostatistics, Boston University, Boston, Massachusetts

92. Department of Psychiatry, Johns Hopkins University, Baltimore, Maryland

93. Department of Preventive Medicine, University of Southern California, Los Angeles

94. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York University, New York

95. Department of Neurology, University of Miami, Miami, Florida

96. Department of Neurosciences, University of California, San Diego, La Jolla120Department of Pathology, University of California, San Diego, La Jolla

97. Northwest Research Group on Aging, School of Nursing, University of Washington, Seattle

98. Cognitive Neurology and Alzheimer’s Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois123Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois

99. Department of Pathology, University of Southern California, Los Angeles

100. Department of Pathology and Immunology, Washington University, St Louis, Missouri125Department of Neurology, Washington University, St Louis, Missouri

101. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis126Department of Medical and Molecular Genetics, Indiana University, Indianapolis

102. Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota128Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota

103. Department of Neurology, Oregon Health & Science University, Portland

104. Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona130Arizona Alzheimer’s Consortium, Phoenix131Banner Alzheimer’s Institute, Phoenix, Arizona

105. Department of Psychiatry, New York University, New York132Alzheimer’s Disease Center, New York University, New York

106. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York95Department of Neurology, Columbia University, New York, New York133Gertrude H. Sergievsky Center, Columbia University, New York, New York

107. Department of Neurology, University of Texas Southwestern Medical Center, Dallas

108. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York

109. Department of Medical and Molecular Genetics, Indiana University, Indianapolis135Department of Radiology and Imaging Sciences, Indiana University, Indianapolis

110. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois136Department of Pathology (Neuropathology), Rush University Medical Center, Chicago, Illinois

111. Department of Neurology, University of Southern California, Los Angeles137Department of Psychiatry, University of Southern California, Los Angeles

112. Department of Neurology, Boston University, Boston, Massachusetts

113. Department of Pathology, Johns Hopkins University, Baltimore, Maryland

114. Geriatric Research, Education, and Clinical Center, VA Puget Sound Healthcare System, Seattle, Washington114Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle

115. Department of Anatomy and Neurobiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington

116. Department of Neurology, University of California, Los Angeles142Department of Pathology and Laboratory Medicine, University of California, Los Angeles

117. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York143Department of Pathology, Columbia University, New York, New York

118. Cognitive Neurology and Alzheimer’s Disease Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois144Department of Psychiatry, Northwestern University Feinberg School of Medicine, Chicago, Illinois

119. Department of Medicine, Duke University, Durham, North Carolina145Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina

120. Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, New York

121. Department of Pathology, Oregon Health & Science University, Portland

122. Evelyn F. McKnight Brain Institute, Department of Neurology, Miller School of Medicine, University of Miami, Miami, Florida

123. Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

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