Biological markers of amyloid beta-related mechanisms in Alzheimer's disease.
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Authors
Hampel, HaraldShen, Yong
Walsh, Dominic M
Aisen, Paul
Shaw, Les M
Zetterberg, Henrik
Trojanowski, John Q
Blennow, Kaj
Affiliation
Discipline of Psychiatry, School of Medicine and Trinity College Institute of, Neuroscience (TCIN), Laboratory of Neuroimaging and Biomarker Research, Trinity, College Dublin, Trinity Centre for Health Sciences, The Adelaide and Meath, Hospital Incorporating The National Children's Hospital (AMiNCH), Dublin,, Ireland; Department of Psychiatry, Alzheimer Memorial Center, Ludwig Maximilian, University, Munich, Germany.Issue Date
2012-02-01T10:47:53ZMeSH
Alzheimer Disease/drug therapy/*metabolism/*pathologyAmyloid beta-Peptides/*metabolism
Biological Markers/*metabolism
Brain/metabolism/pathology
Clinical Trials as Topic/methods
Humans
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Exp Neurol. 2010 Jun;223(2):334-46. Epub 2009 Oct 6.Journal
Experimental neurologyDOI
10.1016/j.expneurol.2009.09.024PubMed ID
19815015Abstract
Recent research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer's disease (AD), which has been translated into an intense, ongoing development of disease-modifying treatments. Most new drug candidates are targeted on inhibiting amyloid beta (Abeta) production and aggregation. In drug development, it is important to co-develop biomarkers for Abeta-related mechanisms to enable early diagnosis and patient stratification in clinical trials, and to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Biomarkers are also requested by regulatory authorities to serve as safety measurements. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include Abeta isoforms (Abeta40/Abeta42), soluble APP isoforms, Abeta oligomers and beta-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on core candidate CSF and plasma Abeta-related biomarkers, and gives a conceptual review on how to implement biomarkers in clinical trials in AD.Language
engISSN
1090-2430 (Electronic)0014-4886 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1016/j.expneurol.2009.09.024
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