Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 59, Issue 1, Pages 85-99Publisher
IOS PRESS
DOI: 10.3233/JAD-170027
Keywords
Alzheimer's disease; apolipoproteins E; dementia; ferritin; genetic profile scores; genome-wide association study; iron; population genetics; transferrin
Categories
Funding
- Wellcome Trust
- Medical Research Council (MRC)
- Alzheimer's Research UK (ARUK)
- Welsh Assembly Government
- Alzheimer's Society
- Ulster Garden Villages
- N. Ireland RD Office
- Royal College of Physicians/Dunhill Medical Trust
- MRC
- Mercer's Institute for Research on Ageing
- Bristol Research into Alzheimer's and Care of the Elderly
- Charles Wolfson Charitable Trust
- NIH grants
- Barnes Jewish Foundation
- Charles and Joanne Knight Alzheimer's Research Initiative
- UCLH/UCL Biomedical Centre
- Lundbeck SA
- German Federal Ministry of Education and Research (BMBF)
- Competence Network Dementia
- Competence Network Degenerative Dementia
- Alfried Krupp von Bohlen und Halbach-Stiftung
- European Union of the Sixth Framework program priority [FP6-2004-LIFESCIHEALTH-5]
- Alzheimer's Research Trust UK
- John and Lucille van Geest Foundation
- NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London, Maudsley NHS Foundation Trust and Kings College London
- Guy's and St Thomas' Charity
- Maudsley Charity
- Academy of Finland
- Kuopio University Hospital
- UEF-BRAIN
- National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre and Dementia Unit at South London and Maudsley NHS Foundation Trust and (Institute of Psychiatry, Psychology and Neuroscience) King's College London
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc.
- Biogen Idec Inc.
- Bristol-Myers Squibb Company
- Eisai Inc.
- Elan Pharmaceuticals, Inc.
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
- Genentech, Inc.
- Fujirebio
- GE Healthcare
- IXICO Ltd.
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Medpace, Inc.
- Merck Co., Inc.
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc.
- Piramal Imaging
- Servier
- Synarc Inc.
- Takeda Pharmaceutical Company
- Canadian Institutes of Health Research
- Wellcome Trust [076113, 085475, 082604/2/07/Z]
- cite the relevant primary WTCCC publication
- Australian National Health and Medical Research Council (NHMRC) [241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485]
- US National Institutes of Health (NIH) [AA07535, AA10248, AA014041, AA011998, AA013320, AA013321, AA017688, DA012854]
- Australian Research Council (ARC) [DP0770096]
- Perpetual Foundation Wilson Fellowship
- Australian National Health and Medical Research Council [APP1084417, APP1079583]
- French National Foundation on Alzheimer's disease and related disorders
- LABEX (laboratory of excellence program investment for the future) DISTALZ grant
- Inserm
- Institut Pasteur de Lille
- Universite de Lille 2
- Lille University Hospital
- Medical Research Council [503480]
- Alzheimer's Research UK [503176]
- German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) [01GI0102, 01GI0711, 01GI0420]
- NIH/NIA grant [R01 AG033193]
- NIA [AG081220]
- AGES [N01-AG-12100]
- NHLBI [R01 HL105756]
- Icelandic Heart Association
- Erasmus Medical Centre
- Erasmus University
- NIH/NIA grants [U01 AG032984, U24 AG021886, U01 AG016976]
- Alzheimer's Association [ADGC-10-196728]
- Alzheimers Research UK [ARUK-SRF2016A-3] Funding Source: researchfish
- Medical Research Council [G1001799, MR/N01104X/2, MR/N01104X/1] Funding Source: researchfish
- Parkinson's UK [J-1403] Funding Source: researchfish
- MRC [MR/N01104X/2, MR/N01104X/1, G1001799] Funding Source: UKRI
Ask authors/readers for more resources
Iron deposition in the brain is a prominent feature of Alzheimer's disease (AD). Recently, peripheral iron measures have also been shown to be associated with AD status. However, it is not known whether these associations are causal: do elevated or depleted iron levels throughout life have an effect onADrisk? We evaluate the effects of peripheral iron onADrisk using a genetic profile score approach by testing whether variants affecting iron, transferrin, or ferritin levels selected from GWAS meta-analysis of approximately 24,000 individuals are also associated with AD risk in an independent case-control cohort (n similar to 10,000). Conversely, we test whether AD risk variants from a GWAS meta-analysis of approximately 54,000 account for any variance in iron measures (n similar to 9,000). We do not identify a genetic relationship, suggesting that peripheral iron is not causal in the initiation of AD pathology.
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