Affecting nearly 36 million people worldwide, Alzheimer’s Disease (AD) is one of the most elusive chronic diseases in terms of diagnosis and treatment. The only definitive way to diagnose Alzheimer’s is through a brain autopsy or post-mortem.
That may change because scientists at Durin Technologies and the University of Medicine and Dentistry of New Jersey have developed a test that can differentiate between the blood sera of those with AD and those in the non-demented control (NDC) group. The test uses a protein microarray to detect a group of 10 autoantibody biomarkers that the researchers showed could be used as specific and accurate indications of AD: It demonstrated a diagnostic sensitivity (detects positives correctly) of 96% and specificity (detects negatives correctly) of 92.5%. In their paper, published recently in PLoS One, the researchers discuss why they chose to focus on autoantibodies and what applications that may have both for diagnosis and the development of therapeutics:
The underlying reason for the presence and abundance of autoantibodies in human sera, especially in younger and healthy individuals, is unknown. Although some autoantibodies may be vestiges of past diseases and reflect a history of immunological activity, it is clear that many are also present as a result of ongoing disease. We suggest that active diseases, resulting in cell damage and death, cause the production and release of antigenic cellular products. In the case of AD, the somewhat selective early loss of pyramidal neurons provides a chronic, yet specific, source of such breakdown products. These products enter the cerebrospinal fluid, diffuse into the blood and lymph, with some presumably acting as antigens to elicit an immune response. We propose that this response leads to the production and appearance of a relatively large number of autoantibodies in the blood. Since many diseases exhibit damage to specific cell and tissue types, the biomarker discovery strategy described here could conceivably be applicable to the development of successful diagnostics for a wide variety of diseases.
One further advantage of using protein microarrays to detect disease-related autoantibodies in sera is that their antigen targets also become known. This knowledge may prove to have therapeutic implications, especially if it sheds new light on disease-relevant pathways. Such information could be used to develop therapies that combat pathology by targeting important members of these pathways. Currently, little is known about the functions of most of the antigens identified here as targets of the autoantibody biomarkers for AD. Many of them are explicit only at the genetic level as elucidated by efforts in creating comprehensive cDNA libraries As more is learned about the functions of autoantibodies in the sera and their targets, we anticipate that a better understanding of autoantibody profiles will eventually yield significant therapeutic benefits.
… The relative non-invasiveness, low cost, and dynamism of protein microarrays make a diagnostic of this kind well-suited for incorporation into routine health care. We hope that with a diagnostic such as this, accessible early screening methods can be established so that patients will be better positioned to avail themselves of effective therapies as they arise.
For the sake of millions of patients worldwide, we hope that this is the real deal and will not be forgotten as one of the many diagnostic tests that never made it into clinical use.
Press Release: Researchers Develop Reliable, Accurate Blood Test for Alzheimer’s Disease
PLoS One Article: Diagnosis of Alzheimer’s Disease Based on Disease-Specific Autoantibody Profiles in Human Sera
Flashback: Skin Test to Diagnose Alzheimer’s
