Alzheimer’s Testing Based on Disease-Specific Autoantibody Profiles in Human Sera
A small set of autoantibody biomarkers in human serum is effective and reliable in distinguishing healthy controls from patients with Alzheimer’s disease, according to a study published in the August PLoS One. These diagnostic indicators could lead to the development of a noninvasive diagnostic test for the disease.
Led by Robert Nagele, PhD, from the School of Osteopathic Medicine at the University of Medicine and Dentistry of New Jersey in Stratford, a group of investigators obtained serum samples from 50 patients with Alzheimer’s disease and 40 nondemented controls; both groups contained earlier- and later-stage patients, as well as younger and older controls.
“We searched for disease group– and control group–specific variations in autoantibody expression patterns in an effort to identify potentially useful diagnostic biomarkers,” they wrote. Using protein microarray analysis, the investigators identified 10 autoantibody biomarkers (from a set of 9,486 antigens) that had a significantly higher prevalence in the Alzheimer’s group than in the control group.
“When the 10 autoantibody markers were used to classify all [90 samples], they did so with a 96.0% sensitivity and a 92.5% specificity,” the authors reported. The researchers also tested their ability to classify samples from different demographics of varying age and disease stage, finding that Alzheimer’s disease samples were correctly and consistently differentiated from younger controls.
“This successful classification of Alzheimer’s disease across the full range of available Mini-Mental State Examination scores suggests that this approach is useful for Alzheimer’s disease diagnosis throughout the full course of the disease, and may also be useful for early detection, perhaps including patients with mild cognitive impairment and presymptomatic disease,” they wrote.
In addition, Dr. Nagele and his colleagues tested the biomarker profile’s ability to distinguish between neurodegenerative diseases that share a similar pathology.
“It was possible to differentiate Alzheimer’s disease samples from Parkinson’s disease samples with over 86% accuracy,” the authors stated. “To our knowledge, this is the highest efficiency ever achieved with blood biomarkers to distinguish these closely related neurodegenerative diseases.”
The results of the current study demonstrate that Alzheimer’s disease can be linked to characteristic changes in serum autoantibody expression profiles, the authors explained. “Future work involving more samples should extend our understanding of autoantibody expression and further optimize diagnostic success…. One further advantage of using protein microarrays to detect disease-related autoantibodies in sera is that their antigen targets also become known,” they continued. “This knowledge may prove to have therapeutic implications, especially if it sheds new light on disease-relevant pathways.
“The relative noninvasiveness, low cost, and dynamism of protein microarrays make a diagnostic of this kind well-suited for incorporation into routine health care,” the authors concluded. “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.”
Suggested Reading
Nagele E, Han M, Demarshall C, et al. Diagnosis of Alzheimer’s disease based on disease-specific autoantibody profiles in human sera. PLoS One. 2011;6(8):e23112.
Nagele RG, Clifford PM, Siu G, et al. Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-b1-42 deposition. J Alzheimers Dis. 2011;25(4):605-622.