期刊
ALZHEIMERS & DEMENTIA
卷 6, 期 3, 页码 230-238出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2010.03.008
关键词
Alzheimer's disease; Cerebrospinal fluid; Plasma; Biomarkers; Mild cognitive impairment
资金
- Alzheimei's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- Abbott
- AstraZeneca AB
- Bayer Schering Pharma AG
- Bristol-Myers Squibb
- Eisai Global Clinical Development
- Elan Corporation
- Genentech
- GE Healthcare
- GlaxoSmithKline
- Innogenetics
- Johnson and Johnson
- Eh Lilly and Co.
- Medpace, Inc.
- Merck and Co. Inc.
- Novartis AG
- Pfizer Inc.
- F. Hoffman-La Roche
- Schering-Plough
- Synarc. Inc.
- Wyeth
- Alzheimer's Association and Alzheimer's Drug Discovery, Foundation
- NIH [P30 AG010129, K01 AG030514]
- Dana Foundation
- Marian S. Ware Alzheimer Program
- [AG 10124]
- NATIONAL INSTITUTE ON AGING [U01AG024904, P30AG010124, P30AG010129, K01AG030514, U19AG010483] Funding Source: NIH RePORTER
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 A beta 1-42 and total tau (T-tau) that effectively delineates mild AD in the large multisite prospective clinical investigation conducted in ADNI This signature appeals 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 A beta 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 lender the biomarkers studied in ADNI more applicable to routine diagnosis and to clinical trials of disease modifying therapies (C) 2010 The Alzheimer's Association All rights reserved
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