Use of biomarkers in clinical trials of Alzheimer disease: from concept to application

Mol Diagn Ther. 2011 Dec 1;15(6):313-25. doi: 10.1007/BF03256467.

Abstract

Research progress during the last decades has resulted in an unprecedented accumulation of knowledge regarding the molecular pathogenesis of Alzheimer disease (AD). These important achievements toward clarifying the mechanistic processes underlying AD are being translated into ongoing development of biomarkers and their use in clinical trials. AD biomarkers are biochemical and anatomical variables (e.g. cerebrospinal fluid, positron emission tomography, and structural MRI) that measure AD-related pathologic features (i.e. amyloid deposition and neurodegeneration) in vivo. Biomarkers are utilized as 'diagnostic biomarkers' and/or 'endpoint biomarkers' in symptomatic or disease-modifying clinical trials. Diagnostic biomarkers play an important role in population enrichment by refining selection criteria, stratifying populations, and increasing the statistical power of trials. Endpoint biomarkers may be used as outcome measures to monitor the rate of disease progression and detect treatment effects. AD biomarkers do not reach abnormal levels or peak simultaneously, but do so in a time-dependent order. The choice of biomarkers for a clinical trial must take into consideration the type of therapeutic intervention, the clinical stage of AD, and the time dependence of biomarker changes during disease progression. The combination of amyloid and neurodegeneration biomarkers is highly desirable since they capture different aspects of the disease. Clinical trials for every clinical stage of AD would benefit from quantification and standardization of biomarkers. However, this is still a work in progress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Biomarkers / metabolism*
  • Clinical Trials as Topic
  • Disease Progression
  • Humans
  • Magnetic Resonance Imaging
  • Positron-Emission Tomography

Substances

  • Biomarkers