Biomarkers for Alzheimer's disease therapeutic trials

被引：98

作者：

Hampel, Harald ^{[1
]}

Wilcock, Gordon ^{[2
]}

Andrieu, Sandrine ^{[3
,4
,5
]}

Aisen, Paul ^{[6
]}

Blennow, Kaj ^{[7
]}

Broich, K. ^{[8
]}

Carrillo, Maria ^{[9
]}

Fox, Nick C. ^{[10
]}

Frisoni, Giovanni B. ^{[11
]}

Isaac, Maria ^{[12
]}

Lovestone, Simon ^{[13
]}

Nordberg, Agneta ^{[14
,15
]}

Prvulovic, David ^{[1
]}

Sampaio, Christina ^{[16
,17
]}

Scheltens, Philip ^{[18
,19
]}

Weiner, Michael ^{[20
]}

Winblad, Bengt ^{[21
]}

Coley, Nicola ^{[3
,4
]}

Vellas, Bruno ^{[3
,4
,22
]}

机构：

[1] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, D-60528 Frankfurt, Germany

[2] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England

[3] INSERM, U558, F-31073 Toulouse, France

[4] Univ Toulouse 3, F-31073 Toulouse, France

[5] CHU Toulouse, Dept Epidemiol & Publ Hlth, F-31073 Toulouse, France

[6] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[7] Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Clin Neurochem Lab,Sahlgrenska Acad, SE-43180 Molndal, Sweden

[8] Fed Inst Drugs & Med Devices BfArM, D-53175 Bonn, Germany

[9] Alzheimers Assoc Natl Off, Alzheimers Assoc, Chicago, IL 60601 USA

[10] UCL Inst Neurol, Dept Neurodegenerat Dis, Dementia Res Ctr, London WC1N 38G, England

[11] IRCCS San Giovanni Dio FBF, Lab Epidemiol & Neuroimaging, I-25123 Brescia, Italy

[12] Inst Psychiat, London, England

[13] Kings Coll London, Inst Psychiat, NIHR Biomed Res Ctr Mental Hlth, London SE5 8AF, England

[14] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Alzheimer Neurobiol, S-10401 Stockholm, Sweden

[15] Karolinska Univ Hosp Huddinge, Dept Geriatr Med, Stockholm, Sweden

[16] Lab Clin Pharmacol & Therapeut, P-1649028 Lisbon, Portugal

[17] Fac Med, Inst Med Mol, P-1649028 Lisbon, Portugal

[18] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands

[19] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands

[20] Univ Calif San Francisco, VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA

[21] Karolinska Inst, Alzheimer Dis Res Ctr, Stockholm, Sweden

[22] CHU Toulouse, Dept Geriatr Med, F-31059 Toulouse, France

来源：

PROGRESS IN NEUROBIOLOGY | 2011年 / 95卷 / 04期

关键词：

Alzheimer's disease; Biomarkers; Neuroimaging; Early diagnosis; MILD COGNITIVE IMPAIRMENT; FLUID AMYLOID-BETA; GAMMA-SECRETASE INHIBITOR; PLACEBO-CONTROLLED TRIAL; SURROGATE END-POINTS; CEREBROSPINAL-FLUID; CSF BIOMARKERS; FOLLOW-UP; DOUBLE-BLIND; A-BETA;

D O I：

10.1016/j.pneurobio.2010.11.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

The development of disease-modifying treatments for Alzheimer's disease requires innovative trials with large numbers of subjects and long observation periods. The use of blood, cerebrospinal fluid or neuroimaging biomarkers is critical for the demonstration of disease-modifying therapy effects on the brain. Suitable biomarkers are those which reflect the progression of AD related molecular mechanisms and neuropathology, including amyloidogenic processing and aggregation, hyperphosphorylation, accumulation of tau and neurofibrillary tangles, progressive functional, metabolic and structural decline, leading to neurodegeneration, loss of brain tissue and cognitive symptoms. Biomarkers should be used throughout clinical trial phases I-III of AD drug development. They can be used to enhance inclusion and exclusion criteria, or as baseline predictors to increase the statistical power of trials. Validated and qualified biomarkers may be used as outcome measures to detect treatment effects in pivotal clinical trials. Finally, biomarkers can be used to identify adverse effects. Questions regarding which biomarkers should be used in clinical trials, and how, are currently far from resolved. The Oxford Task Force continues and expands the work of our previous international expert task forces on disease-modifying trials and on endpoints for Alzheimer's disease clinical trials. The aim of this initiative was to bring together a selected number of key international opinion leaders and experts from academia, regulatory agencies and industry to condense the current knowledge and state of the art regarding the best use of biological markers in Alzheimer's disease therapy trials and to propose practical recommendations for the planning of future AD trials. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：579 / 593

页数：15

共 147 条

[1]

A Phase II study targeting amyloid-β with 3APS in mild-to-moderate Alzheimer disease [J].