Blood-derived disease biomarker of Alzheimer’s disease: tell me what you react to and I’ll tell you who you are

In the August 3 online issue of PLoS One (PLoS One. 2011; 6(8): e23112), Eric Nagele and colleagues report the discovery of a potential new diagnostic biomarker for Alzheimer’s disease (AD) based on the detection of serum autoantibodies specific for a unique set of self-proteins.  This work marks a major step forward in the process of realizing the promises of preventive medicine for this devastating disease.  As I wrote in a previous post, the ability to intervene early in the course of AD is considered to be critical to the success of disease modifying therapies currently under development.  By providing an easily deployable means to screen for individual at risks prior to the onset of clinical manifestation of the disease, this simple blood test has the potential to radically change the disease management practices in AD.

The association of autoantibodies with certain diseases is not new.  Antibodies specific for self-proteins are characteristic of rheumatoid diseases and most cases of multiple sclerosis.  These autoantibodies are generally thought to contribute to the pathobiology of these diseases.  In contrast, the association of autoantibodies with non-immunological diseases is rather intriguing.  It is tempting to speculate that this process could be generalized to other degenerative diseases:  disease states characterized by the release in the body of rare and/or usually sequestered proteins that would be recognized by the immune system as potentially foreign (see principles of immune tolerance).  If this generalization turns out to be valid, one could easily imagine a broad application of autoantibody-based disease diagnostics.  While this hypothesis could potentially open the doors to new applications, it could also constitute a potential obstacle.  If auto-antibodies are broadly associated with degenerative diseases, it might be difficult to distinguish between closely related conditions.  Nagele et al. already addressed part of this potential issue by showing that the subset of autoantibodies specific for AD could distinguish with relative accuracy the sera from AD patients from the sera of patients diagnosed with Parkinson’s disease.  Further analysis of this autoantibody-based biomarker in samples derived from patients at different stages of AD and from patients with different forms of dementia (e.g. vascular dementia, dementia with Lewy bodies) should provide the necessary evidences to qualify this biomarker for practical application.

Thierry Sornasse for Integrated Biomarker Strategy