Nagele E, Han M, Demarshall C, Belinka B, Nagele R.
Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera.
PLoS One. 2011;6(8):e23112.
PubMed.
Genomics and proteomics have become highly active research areas to search for novel genes and proteins involved in disease pathogenesis, or to identify novel biomarkers. Research has also expanded to include other “omics” such as metabolomics and lipidomics. In this PLOS-One paper, Nagele and coworkers now take this one step further, to autoantibodies, which could be called “autoantibody-omics,” if you like the “-omics” ending. They screen human serum samples for autoantibodies against a very large number (>9,000) of proteins and show that serum contains a very high number (>1,000) of such antibodies against proteins. Interestingly, the prevalence of autoantibodies was much higher in sera from AD patients. In the next step, they selected the 10 markers that showed the largest difference between AD and controls, ending up with a close-to-perfect diagnostic accuracy. These autoantibodies were directed against a wide range of proteins, not specifically (at least not as known today) linked to AD pathogenesis.
The data are very promising for a specific biomarker for AD in peripheral blood. But much work is needed before we have such a test in our hands. As pointed out by the authors, a diagnostic test based on multiple indicators is complicated by the fact that many different combinations of biomarkers can be used to distinguish patients from controls with varying diagnostic accuracy. Further, findings from proteomic studies reporting protein panels for use as diagnostic markers have been notoriously difficult to replicate. For these reasons, it will be important to verify the diagnostic utility of these 10 autoantibodies in several independent AD patient and control populations, and also to further study their performance in different clinical stages of AD, as well as in other dementias such as frontotemporal and vascular dementia. Nevertheless, this study thus brings hope for the first blood-based diagnostic test for AD.
Comments
University of Goteborg, Sahlgrenska University Hospital
Genomics and proteomics have become highly active research areas to search for novel genes and proteins involved in disease pathogenesis, or to identify novel biomarkers. Research has also expanded to include other “omics” such as metabolomics and lipidomics. In this PLOS-One paper, Nagele and coworkers now take this one step further, to autoantibodies, which could be called “autoantibody-omics,” if you like the “-omics” ending. They screen human serum samples for autoantibodies against a very large number (>9,000) of proteins and show that serum contains a very high number (>1,000) of such antibodies against proteins. Interestingly, the prevalence of autoantibodies was much higher in sera from AD patients. In the next step, they selected the 10 markers that showed the largest difference between AD and controls, ending up with a close-to-perfect diagnostic accuracy. These autoantibodies were directed against a wide range of proteins, not specifically (at least not as known today) linked to AD pathogenesis.
The data are very promising for a specific biomarker for AD in peripheral blood. But much work is needed before we have such a test in our hands. As pointed out by the authors, a diagnostic test based on multiple indicators is complicated by the fact that many different combinations of biomarkers can be used to distinguish patients from controls with varying diagnostic accuracy. Further, findings from proteomic studies reporting protein panels for use as diagnostic markers have been notoriously difficult to replicate. For these reasons, it will be important to verify the diagnostic utility of these 10 autoantibodies in several independent AD patient and control populations, and also to further study their performance in different clinical stages of AD, as well as in other dementias such as frontotemporal and vascular dementia. Nevertheless, this study thus brings hope for the first blood-based diagnostic test for AD.
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