Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011;6(8):e23112.
doi: 10.1371/journal.pone.0023112. Epub 2011 Aug 3.

Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera

Eric Nagele  1 , Min Han, Cassandra Demarshall, Benjamin Belinka, Robert Nagele
Affiliations

Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera

Eric Nagele et al. PLoS One. 2011.

Abstract

After decades of Alzheimer's disease (AD) research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC) groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: MH and CD have no competing interests. EPN is a paid consultant for Durin Technologies. BB is CEO of Durin Technologies and receives a salary from Durin. He also owns stock in Durin. RGN is Founder of Durin Technologies and has stock interest. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Biomarker selection and Training / Testing Analysis.
Before biomarker selection, our total sample pool was split into two randomized groups: the Training Set and Testing Set. Prospector and PAM statistical analyses were performed on the Training Set to identify the top 10 most significant autoantibody classifiers of AD and NDC. We then verified the diagnostic accuracy of these selected biomarkers by using Random Forest to predict sample classification in the Training Set, Testing Set, and then both sets combined.
Figure 2
Figure 2. Differential Expression of PTCD2 and FRMD8 autoantibodies in AD and NDC sera.
Microarray fluorescence values reflecting individual serum autoantibody titers demonstrate a difference in the expression of anti-PTCD2 and anti-FRMD8 in AD (n = 50) and NDC (n = 40) sera (a,c). This difference was confirmed in independent dot blots that assessed AD and NDC sera reactivity to purified PTCD2 and FRMD8 protein antigens (b,d).
See this image and copyright information in PMC

References

    1. Thies W, Bleiler L. 2011 Alzheimer's disease facts and figures. Alzheimers Dement. 2011;7:208–244. - PubMed
    1. Clifford PM, Zarrabi S, Siu G, Kinsler KJ, Kosciuk MC, et al. Abeta peptides can enter the brain through a defective blood-brain barrier and bind selectively to neurons. Brain Res. 2007;1142:223–236. - PubMed
    1. Di Domenico F, Sultana R, Barone E, Perluigi M, Cini C, et al. Quantitative proteomics analysis of phosphorylated proteins in the hippocampus of Alzheimer's disease subjects. J Proteomics. 2011;74:1091–1103. - PMC - PubMed
    1. Dickson DW. Neuropathological diagnosis of Alzheimer's disease: a perspective from longitudinal clinicopathological studies. Neurobiol Aging. 1997;18:S21–26. - PubMed
    1. Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord. 2005;19:163–165. - PubMed

Publication types