@article{980259c61a81439995e5749d9e0a1cf7,
title = "Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer's disease",
abstract = "Recent evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease. TREM2 mutations are the genetic basis for a condition characterized by polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) and an early-onset dementia syndrome. TREM2 is important in the phagocytosis of apoptotic neuronal cells by microglia in the brain. Loss of function might lead to an impaired clearance and to accumulation of necrotic debris and subsequent neurodegeneration. In this study, we investigated a consanguineous family segregating autosomal recessive behavioral variant FTLD from Antioquia, Colombia. Exome sequencing identified a nonsense mutation in TREM2 (p.Trp198X) segregating with disease. Next, using a cohort of clinically characterized and neuropathologically verified sporadic AD cases and controls, we report replication of the AD risk association at rs75932628 within TREM2 and demonstrate that TREM2 is significantly overexpressed in the brain tissue from AD cases. These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease.",
keywords = "Alzheimer's disease, FTLD, Neurodegeneration, TREM2",
author = "Margarita Giraldo and Francisco Lopera and Siniard, {Ashley L.} and Corneveaux, {Jason J.} and Isabelle Schrauwen and Julian Carvajal and Claudia Mu{\~n}oz and Manuel Ramirez-Restrepo and Chris Gaiteri and Myers, {Amanda J.} and Caselli, {Richard J.} and Kosik, {Kenneth S.} and Reiman, {Eric M.} and Huentelman, {Matthew J.}",
note = "Funding Information: This work was funded in part by COLCIENCIAS : proyect 111554531651, award to FL. IS is a postdoctoral fellow of the FWO-vlaanderen. This work was supported by Kronos Science; The National Institute of Neurological Disorders and Stroke [R01 NS059873 to MJH]; The National Institute on Aging [R01 AG031581 to EMR, P30 AG19610 to EMR, AG034504 to AJM]; The Banner Alzheimer's Foundation ; The Johnnie B. Byrd Sr. Alzheimer's Disease Institute ; The Medical Research Council ; The Intramural Research Program of the National Institutes of Health ; and the state of Arizona. Funding Information: Many data and biomaterials were collected from several National Institute on Aging (NIA) and National Alzheimer's Coordinating Center (NACC, grant #U01 AG016976) funded sites. Amanda J. Myers, PhD (University of Miami, Department of Psychiatry) and John A. Hardy, PhD (Reta Lila Weston Institute, University College London) collected and prepared the series. Marcelle Morrison-Bogorad, PhD., Tony Phelps, PhD and Walter Kukull PhD are thanked for helping to co-ordinate this collection. The directors, pathologist and technicians involved include: National Institute on Aging: Ruth Seemann, John Hopkins Alzheimer's Disease Research Center (NIA grant # AG05146): Juan C. Troncoso, MD, Dr Olga Pletnikova, University of California, Los Angeles (NIA grant # P50 AG16570):Harry Vinters, MD, Justine Pomakian, The Kathleen Price Bryan Brain Bank, Duke University Medical Center (NIA grant #AG05128, NINDS grant # NS39764, NIMH MH60451 also funded by Glaxo Smith Kline): Christine Hulette, MD, Director, John F. Ervin, Stanford University: Dikran Horoupian, MD, Ahmad Salehi, MD, PhD, New York Brain Bank, Taub Institute, Columbia University (NYBB): Jean Paul Vonsattel, MD, Katerina Mancevska, Massachusetts Alzheimer's Disease Research Center (P50 AG005134): E. Tessa Hedley-Whyte, MD, MP Frosch, MD, Karlotta Fitch, University of Michigan (NIH grant P50-AG08671): Dr Roger Albin, Lisa Bain, Eszter Gombosi, University of Kentucky (NIH #AG05144): William Markesbery, MD, Sonya Anderson, Mayo Clinic, Jacksonville: Dennis W. Dickson, MD, Natalie Thomas, University Southern California: Caroll A. Miller, MD, Jenny Tang, M.S., Dimitri Diaz, Washington University, St Louis Alzheimer's Disease Research Center (NIH #P50AG05681): Dan McKeel, MD, John C. Morris, MD, Eugene Johnson, Jr, PhD, Virginia Buckles, PhD, Deborah Carter, University of Washington, Seattle (NIH #P50 AG05136):Thomas Montine, MD, PhD, Aimee Schantz, MEd, University of Pennsylvania School of Medicine, Alzheimer's Disease Research Center: John Q Trojanowski, MD, Virginia M Lee, MD, Vivianna Van Deerlin, MD, Terry Schuck, Boston University Alzheimer's Disease Research Center (NIH grant P30-AG13846): Ann C. McKee, Carol Kubilus Sun Health Research Institute Brain Donation Program of Sun City, Arizona (NIA #P30 AG19610; Arizona Alzheimer's Disease Core Center, Arizona Department of Health Services, contract 211002, Arizona Alzheimer's Research Center; Arizona Biomedical Research Commission, contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium; Michael J. Fox Foundation for Parkinson's Research): Joseph Rogers, PhD, Thomas G. Beach, MD, PhD, Lucia I. Sue Emory University: Bruce H. Wainer, MD, PhD, Marla Gearing, PhD, University of Texas, Southwestern Medical School: Charles L. White, III, M.D., Roger Rosenberg, Marilyn Howell, Joan Reisch, University of California, Davis: William Ellis, MD, Mary Ann Jarvis, Rush University Medical Center, Rush Alzheimer's Disease Center (NIH #AG10161): David A. Bennett, M.D. Julie A. Schneider, MD, MS, Karen Skish, MS, PA (ASCP)MT, Wayne T Longman, University of Miami/NPF Brain Endowment Bank: Deborah C. Mash, MD, Margaret J Basile, Mitsuko Tanaka Oregon Health & Science University: Randy Wotljer, PhD. Additional tissues include samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts and Newcastle University): C.M. Morris, MD, Ian G McKeith, Robert H Perry MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council): Simon Lovestone, Md PhD, Safa Al-Sarraj. MD, Claire Troakes, South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer's Research Trust (ART), BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN): Seth Love, MD, Patrick Kehoe, PhD, Laura Palmer, The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek): Inge Huitinga, MD, Marleen Rademaker, Michiel Kooreman, Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona: Isidre Ferrer Abizanda, MD, PhD, Susana Casas Boluda.",
year = "2013",
month = aug,
doi = "10.1016/j.neurobiolaging.2013.02.016",
language = "English (US)",
volume = "34",
pages = "2077.e11--2077.e18",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "8",
}