Advances in the Discovery of Biomarkers for Alzheimer’s Disease

This report describes current thinking regarding the temporal relationship of asymptomatic disease, MCI, and fully established Alzheimer's disease. Biomarkers that can identify individuals at risk will allow therapeutic intervention at the earliest stages. Next-generation "omics" technologies have identified potential multiplex markers as diagnostic aids and prognostic markers in blood and CSF.

Features and benefits

• Gain insight into the current thinking in AD research with regard to the temporal association of biomarkers with disease progression.
• Compare the opportunities provided by different biological fluids, including CSF, blood, saliva, and urine as sources of biomarkers in AD.
• Assess advances in the use of imaging technologies, including MRI and PET as diagnostic and prognostic tools.
• Evaluate the role played by cognitive testing, especially in computer-based formats and in combination with "omic" and imaging technologies.
• Understand the critical importance of developing tests amenable to mass employment, and the importance of biomarkers

Highlights

Aβ42 and tau protein are accepted biomarkers in CSF and can be used to confirm the diagnosis of AD and to differentiate from other dementias. They have also achieved regulatory acceptance for clinical trial enrichment. Aβ42 and/or tau in blood are not suitable as biomarkers.

Multiple individual proteins and genes associated with sporadic AD have been identified but these are not necessarily adequate as biomarkers. Both gene and protein multiplex assays based on next-generation technologies have provided potential multiplex panels that are in development as diagnostic and prognostic tools.

Progress with multiplex panels using blood-based tests on relevant omics platforms has been outstanding. Together with computer-based cognitive testing, these may provide a testing regime applicable to large populations, enabling therapeutic intervention at the earliest time in the AD progression and the best chance of therapeutic effect.

Your key questions answered

• Which biomarkers look most promising for diagnosis of the very earliest signs of disease and for following progression from healthy to MCI to AD?
• What contribution can imaging make to the diagnosis of AD and to predicting progression from MCI to AD?
• What is the relative potential of CSF, blood, saliva, and urine in providing a suitable biomarker for AD?
• What are the prospects for identifying at-risk subjects early enough to initiate disease prevention/modification therapy?
• Is the beta-amyloid hypothesis as important in biomarker research as it has been in efforts to develop therapies for AD?

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