TY - JOUR
T1 - The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study
T2 - A resource for genetic discovery
AU - Reyes-Dumeyer, Dolly
AU - Faber, Kelley
AU - Vardarajan, Badri
AU - Goate, Alison
AU - Renton, Alan
AU - Chao, Michael
AU - Boeve, Brad
AU - Cruchaga, Carlos
AU - Pericak-Vance, Margaret
AU - Haines, Jonathan L.
AU - Rosenberg, Roger
AU - Tsuang, Debby
AU - Sweet, Robert A.
AU - Bennett, David A.
AU - Wilson, Robert S.
AU - Foroud, Tatiana
AU - Mayeux, Richard
N1 - Funding Information:
The following authors have no relevant conflicts of interest to report: Dolly Reyes, Kelley Faber, and Dr. Chao. Dr. Vardarajan has grants from the National Institute on Aging (NIA) of the National Institutes of Health and the Department of Defense and is a consultant to Kodikaz Therapeutics. Dr. Goate has grants from the NIA/NIH and receives money from Athena Diagnostics for licensing of TDP43 mutations, and has consulted for UK Dementia Research Institute, UK VIB, Katholik University, Leuven, Belgium Center for Molecular Neurology, Antwerp, Belgium Queensland Brain Institute, Brisbane, Australia. Dr. Renton has grants from the NIA/NIH, the Alzheimer's Association, and from the JPB Foundation. Dr. Boeve has grants from the NIH, receives royalties as a co‐editor of a textbook on dementia, and is on the Scientific Advisory Board (SAB) for the Tau Consortium. Dr. Rosenberg has grants from the NIA/NIH and The Zale Foundation and receives license/royalty fees from Elsevier Publishing Inc., Springer Publishing Inc.; payments from Elsevier, Springer and Vitruvian, Inc., and The American Academy of Neurology; and he has a 2009 patent on an Amyloid Beta Gene vaccine. Dr. Tsuang has grants from the NIA/NIH and receives consulting fees from Acadia Pharma and is on the SAB for the Lewy Body Association. Dr. Sweet has grants from the NIA/NIH and National Institute of Mental Health of the NIH. Dr. Bennett has grants from the NIA/NIH and the NeuroVision Institution, and consulting relationships with AbbVie Inc., Takeda Pharma, and Origent Data Sciences. Drs. Cruchaga, Pericak‐Vance, Haines, and Wilson have grants from the NIH. Dr. Foroud has grants from the NIA/NIH, The Department of Defense, and the Michael J. Fox Foundation; is on the SAB for several academic institutions; and receives support from Northwestern University for Continuing Medical Education. Dr. Mayeux has grants from the NIA/NIH and is on the SAB for the Rush Alzheimer's Disease Research Center.
Funding Information:
The NIA-LOAD FBS supported the collection of samples used in this study through National Institute on Aging (NIA) grants U24AG026395, U24AG021886, R01AG041797, and U24AG056270. Additional families were contributed to the NIA-LOAD FBS through NIH grants: R01AG028786, R01AG027944, RO1AG027944, RF1AG054074, U01AG052410. We thank contributors, including the Alzheimer's Disease Centers who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. We also thank Cory G. Weinfeld who helped with the analysis of the effects of APOE variability on age at onset of Alzheimer's disease, and created the related figures in the supplemental data.
Publisher Copyright:
© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2022/10
Y1 - 2022/10
N2 - Introduction: The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of Alzheimer's disease (AD). Methods: Recruitment focused on families with two living affected siblings and a third first-degree relative similar in age with or without dementia. Uniform assessments were completed, DNA was obtained, as was neuropathology, when possible. Apolipoprotein E (APOE) genotypes, genome-wide single nucleotide polymorphism (SNP) arrays, and sequencing was completed in most families. Results: APOE genotype modified the age-at-onset in many large families. Novel variants and known variants associated with early- and late-onset AD and frontotemporal dementia were identified supporting an international effort to solve AD genetics. Discussion: The NIA-LOAD FBS is the largest collection of familial AD worldwide, and data or samples have been included in 123 publications addressing the genetic etiology of AD. Genetic heterogeneity and variability in the age-at-onset provides opportunities to investigate the complexity of familial AD.
AB - Introduction: The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study (NIA-LOAD FBS) was established to study the genetic etiology of Alzheimer's disease (AD). Methods: Recruitment focused on families with two living affected siblings and a third first-degree relative similar in age with or without dementia. Uniform assessments were completed, DNA was obtained, as was neuropathology, when possible. Apolipoprotein E (APOE) genotypes, genome-wide single nucleotide polymorphism (SNP) arrays, and sequencing was completed in most families. Results: APOE genotype modified the age-at-onset in many large families. Novel variants and known variants associated with early- and late-onset AD and frontotemporal dementia were identified supporting an international effort to solve AD genetics. Discussion: The NIA-LOAD FBS is the largest collection of familial AD worldwide, and data or samples have been included in 123 publications addressing the genetic etiology of AD. Genetic heterogeneity and variability in the age-at-onset provides opportunities to investigate the complexity of familial AD.
UR - http://www.scopus.com/inward/record.url?scp=85122147315&partnerID=8YFLogxK
U2 - 10.1002/alz.12514
DO - 10.1002/alz.12514
M3 - Article
AN - SCOPUS:85122147315
SN - 1552-5260
VL - 18
SP - 1889
EP - 1897
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 10
ER -