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Making a BioMark on Alzheimer Disease
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Our thanks to Practical Neurology for granting permission to reprint the full text of a recent article (.pdf) by John Trojanowski.
John Trojanowski, Les Shaw, and Anne Fagan led this live discussion on 1 June 2005. Readers are invited to submit additional comments by using our Comments form at the bottom of the page.
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 View Transcript of Live Discussion — Posted 1 June 2005
Review of concept
During the last 15 years or so, we have seen considerable advances in our understanding of the biology of Alzheimer disease (AD). Amyloid-β and phosphorylated tau, the major components of amyloid plaques and neurofibrillary tangles, respectively, have been identified, as have enzymes that are required in their production, such as the γ- and β-secretases and tau kinases like GSK3β. Potential risk factors, such as apolipoprotein E variants, IDE polymorphisms, and homocysteine have also been revealed, and great strides have been made in structural and functional brain imaging techniques. The stage is now set to translate these advances into tests that will aid in the diagnosis of AD.
But AD can begin long before there are any overt symptoms. What would really make an impact is the discovery of an antecedent chemical biomarker, one that would predict, with appreciable certainty, who will get AD, much like the different forms of cholesterol can predict who will get cardiovascular disease.
Currently, there are no biological fluid analytes that would seem to make good antecedent biomarkers. But with the Alzheimer Disease Neuroimaging Initiative (ADNI) (see ARF related news story), and numerous academic and private research labs around the globe hunting for AD biomarkers, that may soon change. However, there are still challenges. How should potential biomarkers be validated and what are the most promising candidates? How should data be collected, analyzed, standardized? What new technologies can accelerate the search?
Read John Trojanowski's recent review in Practical Neurology, then join us for our live forum. We anticipate a discussion that focuses mostly on the scope, goals, and logistics of the biomarker core of ADNI and other biomarker initiatives. Potential topics for discussion include:
- What is the impact of variability in clinical evaluation and diagnostic methods in our search for biomarkers?
- Must we adopt universal methodologies for measuring specific candidate markers (e.g., specific antibodies and ELISA protocols), or are there alternative strategies that will permit meaningful comparisons to be made among data obtained by different methods in different labs?
- Is the concept of a central repository (i.e., a "tissue bank") feasible or even useful?
- What way(s) would be best to manage and disseminate all the eventual biomarker data collected from around the country/world?
- Is there a place for defined incentives for researchers to adopt certain collection and analytical protocols (e.g., funding, data, or collaboration access)?
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