@article{7b24c2b0b6324e949b6e1da2bc5d8871,
title = "Update on the biomarker core of the Alzheimer's Disease Neuroimaging Initiative subjects",
abstract = "Here, we review progress by the Penn Biomarker Core in the Alzheimer's Disease Neuroimaging Initiative (ADNI) toward developing a pathological cerebrospinal fluid (CSF) and plasma biomarker signature for mild Alzheimer's disease (AD) as well as a biomarker profile that predicts conversion of mild cognitive impairment (MCI) and/or normal control subjects to AD. The Penn Biomarker Core also collaborated with other ADNI Cores to integrate data across ADNI to temporally order changes in clinical measures, imaging data, and chemical biomarkers that serve as mileposts and predictors of the conversion of normal control to MCI as well as MCI to AD, and the progression of AD. Initial CSF studies by the ADNI Biomarker Core revealed a pathological CSF biomarker signature of AD defined by the combination of Aβ1-42 and total tau (T-tau) that effectively delineates mild AD in the large multisite prospective clinical investigation conducted in ADNI. This signature appears to predict conversion from MCI to AD. Data fusion efforts across ADNI Cores generated a model for the temporal ordering of AD biomarkers which suggests that Aβ amyloid biomarkers become abnormal first, followed by changes in neurodegenerative biomarkers (CSF tau, F-18 fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging) with the onset of clinical symptoms. The timing of these changes varies in individual patients due to genetic and environmental factors that increase or decrease an individual's resilience in response to progressive accumulations of AD pathologies. Further studies in ADNI will refine this model and render the biomarkers studied in ADNI more applicable to routine diagnosis and to clinical trials of disease modifying therapies.",
keywords = "Alzheimer's disease, Biomarkers, Cerebrospinal fluid, Mild cognitive impairment, Plasma",
author = "Trojanowski, {John Q.} and Hugo Vandeerstichele and Magdalena Korecka and Clark, {Christopher M.} and Aisen, {Paul S.} and Petersen, {Ronald C.} and Kaj Blennow and Holly Soares and Adam Simon and Piotr Lewczuk and Robert Dean and Eric Siemers and Potter, {William Z.} and Weiner, {Michael W.} and Jack, {Clifford R.} and William Jagust and Toga, {Arthur W.} and Lee, {Virginia M.Y.} and Shaw, {Leslie M.}",
note = "Funding Information: We thank our ADNI colleagues for their contributions to the work summarized here. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org >). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514 , and the Dana Foundation . Other support has come from AG10124 and the Marian S. Ware Alzheimer Program. VMYL is the John H. Ware III Professor for Alzheimer's Disease Research and JQT is the William Maul Measy-Truman G. Schnabel Jr. M.D. Professor of Geriatric Medicine and Gerontology. We thank Michal Figurski for help with the statistical analyses. We are grateful to Christopher M. Clark, University of Pennsylvania Medical Center, Anne Fagan, Washington University, Hiroyuki Arai, Tohuku University and Holly Soares, Pfizer Global Research and Development, for providing aliquots of non-ADNI CSF samples to prepare the CSF quality control pools used in the immunoassay system employed in this investigation. We thank Donald Baldwin and the Molecular Diagnosis Genotyping Facility at the University of Pennsylvania Medical Center for provision of the APOE genotyping data.",
year = "2010",
month = may,
doi = "10.1016/j.jalz.2010.03.008",
language = "English (US)",
volume = "6",
pages = "230--238",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "3",
}