Amyloid and Tau Biomarkers in CSF.

The journal of prevention of Alzheimer's disease(2015)

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摘要
The number of failed Alzheimer's disease (AD) clinical trials on Aβ-targeting drugs is increasing. The explanation for this is most likely multi-factorial. An optimistic standpoint is that trials have to be on patients in an earlier stage of the disease, before neurodegeneration is too severe, to show efficacy, and probably also of longer duration. Further, there is a general agreement that enrolled patients have to be diagnosed based on combined clinical and biomarker criteria, to avoid noise from the large proportion (20%) of cases that are misdiagnosed if only clinical criteria are used. Last, the poor predictive power of translating an "anti-Aβ" or "anti-plaque" effect from AD transgenic animal models to AD patients also calls for biomarkers to verify target engagement in man, and to show downstream effects of Aβ-targeting drug candidates in AD patients. The focus of this review is on the possible role of cerebrospinal fluid (CSF) biomarkers in AD clinical trials for diagnostics, and thus patient enrichment, and for theragnostics, to provide evidence of target engagement of the drug on Aβ metabolism or aggregation, and of effects on the molecular pathology of the disease.
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关键词
Alzheimer’s disease,Biomarker,Cerebrospinal fluid,Clinical trial,Diagnosis,Mild cognitive impairment (MCI),Phosphorylated tau,Plasma,Theragnostic,tau protein,β-amyloid (Aβ)
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