CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology

Elizabeth M Bradshaw; Lori B Chibnik; Brendan T Keenan; Linda Ottoboni; Towfique Raj; Anna Tang; Laura L Rosenkrantz; Selina Imboywa; Michelle Lee; Alina Von Korff; Alzheimer Disease Neuroimaging Initiative; Martha C Morris; Denis A Evans; Keith Johnson; Reisa A Sperling; Julie A Schneider; David A Bennett; Philip L De Jager

doi:10.1038/nn.3435

CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology

Nat Neurosci. 2013 Jul;16(7):848-50. doi: 10.1038/nn.3435. Epub 2013 May 23.

Authors

Elizabeth M Bradshaw¹, Lori B Chibnik, Brendan T Keenan, Linda Ottoboni, Towfique Raj, Anna Tang, Laura L Rosenkrantz, Selina Imboywa, Michelle Lee, Alina Von Korff; Alzheimer Disease Neuroimaging Initiative; Martha C Morris, Denis A Evans, Keith Johnson, Reisa A Sperling, Julie A Schneider, David A Bennett, Philip L De Jager

Collaborators

Alzheimer Disease Neuroimaging Initiative:
Michael W Weiner, Paul Aisen, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R Jack Jr, William Jagust, John Q Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Andrew J Saykin, John Morris, Leslie M Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Robert C Green, Tom Montine, Ronald Petersen, Paul Aisen, Ronald G Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Laurel Beckett, Danielle Harvey, Michael Donohue, Clifford R Jack Jr, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCArli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, William Jagust, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Chet Mathis, Susan Landau, John C Morris, Nigel J Cairns, Erin Householder, Lisa Taylor-Reinwald, Leslie M Shaw, John Q Trojanowki, Virginia Lee, Magdalena Korecka, Michal Figurski, Arthur W Toga, Karen Crawford, Scott Neu, Andrew J Saykin, Tatiana M Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Michael W Weiner, Lean Thal, Zaven Khachaturian, Leon Thal, Neil Buckholtz, Michael W Weiner, Peter J Snyder, William Potter, Steven Paul, Marylyn Albert, Richard Frank, Zaven Khachaturian, John Hsiao, Jeffrey Kaye, Joseph Quinn, Betty Lind, Raina Carter, Sara Dolen, Lon S Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L Heidebrink, Joanne L Lord, Ronald Petersen, Sara S Mason, Colleen S Albers, David Knopman, Kris Johnson, Rachelle S Doody, Javier Villanueva-Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S Honig, Karen L Bell, Beau Ances, John C Morris, Maria Carroll, Sue Leon, Erin Householder, Mark A Mintun, Stacy Schneider, Angela Oliver, Daniel Marson, Randall Griffith, David Clark, David Geldmacher, John Brockington, Erik Roberson, Hillel Grossman, Effie Mitsis, Leyla deToledo-Morrell, Raj C Shah, Ranjan Duara, Daniel Varon, Maria T Greig, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Daniel D'Agostino 2nd, Stephanie Kielb, James E Galvin, Dana M Pogorelec, Brittany Cerbone, Christina A Michel, Henry Rusinek, Mony J de Leon, Lidia Glodzik, Susan De Santi, P Murali Doraiswamy, Jeffrey R Petrella, Terence Z Wong, Steven E Arnold, Jason H Karlawish, David Wolk, Charles D Smith, Greg Jicha, Peter Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad, Oscar L Lopez, MaryAnn Oakley, Donna M Simpson, Anton P Porsteinsson, Bonnie S Goldstein, Kim Martin, Kelly M Makino, M Saleem Ismail, Connie Brand, Ruth A Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Ramon Diaz-Arrastia, Richard King, Myron Weiner, Kristen Martin-Cook, Michael DeVous, Allan I Levey, James J Lah, Janet S Cellar, Jeffrey M Burns, Heather S Anderson, Russell H Swerdlow, Liana Apostolova, Kathleen Tingus, Ellen Woo, Daniel H S Silverman, Po H Lu, George Bartzokis, Neill R Graff-Radford, Francine Parfitt, Tracy Kendall, Heather Johnson, Martin R Farlow, Ann Marie Hake, Brandy R Matthews, Scott Herring, Cynthia Hunt, Christopher H van Dyck, Richard E Carson, Martha G MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Diana Kerwin, Marek-Marsel Mesulam, Kristine Lipowski, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A Sperling, Keith A Johnson, Gad Marshall, Meghan Frey, Jerome Yesavage, Joy L Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan N Sabbagh, Christine M Belden, Sandra A Jacobson, Sherye A Sirrel, Neil Kowall, Ronald Killiany, Andrew E Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O Obisesan, Saba Wolday, Joanne Allard, Alan Lerner, Paula Ogrocki, Leon Hudson, Evan Fletcher, Owen Carmichael, John Olichney, Charles DeCarli, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Steven G Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W Scharre, Maria Kataki, Anahita Adeli, Earl A Zimmerman, Dzintra Celmins, Alice D Brown, Godfrey D Pearlson, Karen Blank, Karen Anderson, Robert B Santulli, Tamar J Kitzmiller, Eben S Schwartz, Kaycee M Sink, Jeff D Williamson, Pradeep Garg, Franklin Watkins, Brian R Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J Rosen, Bruce L Miller, Jacobo Mintzer, Kenneth Spicer, David Bachman, Elizabether Finger, Stephen Pasternak, Irina Rachinsky, John Rogers, Andrew Kertesz, Dick Drost, Nunzio Pomara, Raymundo Hernando, Antero Sarrael, Susan K Schultz, Laura L Boles Ponto, Hyungsub Shim, Karen Elizabeth Smith, Norman Relkin, Gloria Chaing, Lisa Raudin, Amanda Smith, Kristin Fargher, Balebail Ashok Raj

Affiliation

¹ Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

PMID: 23708142
PMCID: PMC3703870
DOI: 10.1038/nn.3435

Abstract

In our functional dissection of the CD33 Alzheimer's disease susceptibility locus, we found that the rs3865444(C) risk allele was associated with greater cell surface expression of CD33 in the monocytes (t50 = 10.06, P(joint) = 1.3 × 10(-13)) of young and older individuals. It was also associated with diminished internalization of amyloid-β 42 peptide, accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging, and increased numbers of activated human microglia.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Age Factors
Aged
Aged, 80 and over
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / genetics
Alzheimer Disease / pathology*
Amyloid beta-Peptides / metabolism*
Aniline Compounds
Brain / diagnostic imaging
Brain / pathology
Cognitive Dysfunction / metabolism
Cognitive Dysfunction / pathology
Cohort Studies
Dextrans / metabolism
Female
Genetic Association Studies
Genotype
HLA-D Antigens / metabolism
Humans
Male
Microglia / pathology
Middle Aged
Monocytes / metabolism*
Peptide Fragments / metabolism*
Plaque, Amyloid / pathology
Polymorphism, Genetic / genetics
Radionuclide Imaging
Sialic Acid Binding Ig-like Lectin 3 / genetics
Sialic Acid Binding Ig-like Lectin 3 / metabolism*
Thiazoles
Young Adult

Substances

2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Amyloid beta-Peptides
Aniline Compounds
Dextrans
HLA-D Antigens
Peptide Fragments
Sialic Acid Binding Ig-like Lectin 3
Thiazoles
amyloid beta-protein (1-42)

Abstract

Publication types

MeSH terms

Substances

Grants and funding