Rarity of the Alzheimer disease-protective APP A673T variant in the United States.

Publication Type:

Journal Article

Authors:

Wang, Li-San; Naj, Adam C; Graham, Robert R; Crane, Paul K; Kunkle, Brian W; Cruchaga, Carlos; Murcia, Josue D Gonzalez; Cannon-Albright, Lisa; Baldwin, Clinton T; Zetterberg, Henrik; Blennow, Kaj; Kukull, Walter A; Faber, Kelley M; Schupf, Nicole; Norton, Maria C; Tschanz, JoAnn T; Munger, Ronald G; Corcoran, Christopher D; Rogaeva, Ekaterina; Lin, Chiao-Feng; Dombroski, Beth A; Cantwell, Laura B; Partch, Amanda; Valladares, Otto; Hakonarson, Hakon; St George-Hyslop, Peter; Green, Robert C; Goate, Alison M; Foroud, Tatiana M; Carney, Regina M; Larson, Eric B; Behrens, Timothy W; Kauwe, John S K; Haines, Jonathan L; Farrer, Lindsay A; Pericak-Vance, Margaret A; Mayeux, Richard; Schellenberg, Gerard D; Albert, Marilyn S; Albin, Roger L; Apostolova, Liana G; Arnold, Steven E; Barber, Robert; Barmada, Michael; Barnes, Lisa L; Beach, Thomas G; Becker, James T; Beecham, Gary W; Beekly, Duane; Bennett, David A; Bigio, Eileen H; Bird, Thomas D; Blacker, Deborah; Boeve, Bradley F; Bowen, James D; Boxer, Adam; Burke, James R; Buxbaum, Joseph D; Cairns, Nigel J; Cao, Chuanhai; Carlson, Chris S; Carroll, Steven L; Chui, Helena C; Clark, David G; Cribbs, David H; Crocco, Elizabeth A; DeCarli, Charles; DeKosky, Steven T; Demirci, F Yesim; Dick, Malcolm; Dickson, Dennis W; Duara, Ranjan; Ertekin-Taner, Nilufer; Fallon, Kenneth B; Farlow, Martin R; Ferris, Steven; Frosch, Matthew P; Galasko, Douglas R; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; Glass, Jonathan D; Graff-Radford, Neill R; Growdon, John H; Hamilton, Ronald L; Hamilton-Nelson, Kara L; Harrell, Lindy E; Head, Elizabeth; Honig, Lawrence S; Hulette, Christine M; Hyman, Bradley T; Jarvik, Gail P; Jicha, Gregory A; Jin, Lee-Way; Jun, Gyungah; Jun, Gyungah; Kamboh, M Ilyas; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Koo, Edward H; Kowall, Neil W; Kramer, Joel H; LaFerla, Frank M; Lah, James J; Leverenz, James B; Levey, Allan I; Li, Gei; Lieberman, Andrew P; Lopez, Oscar L; Lunetta, Kathryn L; Lyketsos, Constantine G; Mack, Wendy J; Marson, Daniel C; Martin, Eden R; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, W Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Montine, Thomas J; Morris, John C; Murrell, Jill R; Olichney, John M; Parisi, Joseph E; Perry, William; Peskind, Elaine; Petersen, Ronald C; Pierce, Aimee; Poon, Wayne W; Potter, Huntington; Quinn, Joseph F; Raj, Ashok; Raskind, Murray; Reiman, Eric M; Reisberg, Barry; Reitz, Christiane; Ringman, John M; Roberson, Erik D; Rosen, Howard J; Rosenberg, Roger N; Sano, Mary; Saykin, Andrew J; Schneider, Julie A; Schneider, Lon S; Seeley, William W; Smith, Amanda G; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Tanzi, Rudolph E; Thornton-Wells, Tricia A; Trojanowski, John Q; Troncoso, Juan C; Tsuang, Debby W; Van Deerlin, Vivianna M; Van Eldik, Linda J; Vardarajan, Badri N; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Williamson, Jennifer; Wishnek, Sarah; Woltjer, Randall L; Wright, Clinton B; Younkin, Steven G; Yu, Chang-En; Yu, Lei

Source:

JAMA neurology, Volume 72, Issue 2, p.209-16 (2015)

Keywords:

Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Protein Precursor, Case-Control Studies, Female, Genotype, Humans, Male, Pedigree, Protective Factors, Sweden, United States

Abstract:

Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.