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Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

Abstract

A molecular test for Alzheimer's disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimer's and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimer's disease 2–6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimer's disease.

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Figure 1: Study outline, clustering of training set, and predictor discovery.
Figure 2: Classification and prediction of clinical Alzheimer's diagnosis in subjects with Alzheimer's disease or MCI and functional analysis of the 18 predictive plasma signaling proteins.

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Acknowledgements

We are grateful to the individuals who participated in this study. We also thank W. Hueber for critical reading and helpful comments on the manuscript, and numerous unnamed staff of our institutions for their efforts in subject recruitment, diagnostic assessment and blood processing. This study was supported by the John Douglas French Alzheimer's Foundation (T.W.-C.), the Alzheimer's Association (T.W.-C.), the US National Institute on Aging (T.W.-C., AG20603; J.A.K., J.F.Q., AG08017; D.R.G., AG05131) and Satoris, Inc. We also acknowledge the support of the Veterans Administration Mental Illness Research, Education and Clinical Center and the various Alzheimer's Centers sponsored by the US National Institute on Aging.

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Contributions

Experiments were coordinated by S.R., M.B. and T.W.-C. Filter array experiment was done by S.R. with the help of C.H. Cytokine antibody array experiments, cluster analysis and class prediction were done by S.R. with scientific advice from R.T. Computational analysis of functional annotations was done by M.B. and T.W.-C. Blood processing, sample preparation, ELISA, subject data collection and administration was done by M.B. with the help of Y.T.-U. Recruitment of patients and control individuals, disease assessment and blood processing in center-coordinated studies was directed or done by A.B., K.B., L.F.F. D.R.G., M.J., A.K., J.A.K, J.L., B.L.M., L.M., J.F.Q., G.D.R., W.H.R., M.N.S., Y.T.S., D.L.S., M.T., J.T. and J.A.Y. The project was conceived by S.R. and T.W.-C. and scientifically directed by T.W.-C., and the paper written by M.B., T.W.-C. and S.R.

Corresponding author

Correspondence to Tony Wyss-Coray.

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Competing interests

Sandip Ray and Charles Herbert are employees of Satoris, Inc. Robert Tibshirani is a consultant for Satoris, Inc. Tony Wyss-Coray is a co-founder and consultant of Satoris, Inc.

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Supplementary Methods, Supplementary References, Supplementary Figs. 1–4, Supplementary Tables 1–3 (PDF 1350 kb)

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Ray, S., Britschgi, M., Herbert, C. et al. Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins. Nat Med 13, 1359–1362 (2007). https://doi.org/10.1038/nm1653

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