Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology

Martina Sattlecker; Steven J Kiddle; Stephen Newhouse; Petroula Proitsi; Sally Nelson; Stephen Williams; Caroline Johnston; Richard Killick; Andrew Simmons; Eric Westman; Angela Hodges; Hilkka Soininen; Iwona Kłoszewska; Patrizia Mecocci; Magda Tsolaki; Bruno Vellas; Simon Lovestone; AddNeuroMed Consortium; Richard J B Dobson

doi:10.1016/j.jalz.2013.09.016

Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology

Alzheimers Dement. 2014 Nov;10(6):724-34. doi: 10.1016/j.jalz.2013.09.016. Epub 2014 Apr 25.

Authors

Martina Sattlecker¹, Steven J Kiddle¹, Stephen Newhouse¹, Petroula Proitsi¹, Sally Nelson², Stephen Williams², Caroline Johnston¹, Richard Killick¹, Andrew Simmons¹, Eric Westman¹, Angela Hodges¹, Hilkka Soininen³, Iwona Kłoszewska⁴, Patrizia Mecocci⁵, Magda Tsolaki⁶, Bruno Vellas⁷, Simon Lovestone¹; AddNeuroMed Consortium; Richard J B Dobson⁸

Affiliations

¹ King's College London, Institute of Psychiatry, London, UK; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK.
² SomaLogic, Boulder, CO, USA.
³ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁴ Medical University of Lodz, Lodz, Poland.
⁵ Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
⁶ 3rd Department of Neurology, Aristotle University, Thessaloniki, Greece.
⁷ INSERM U 558, University of Toulouse, Toulouse, France.
⁸ King's College London, Institute of Psychiatry, London, UK; NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation Trust, London, UK. Electronic address: richard.j.dobson@kcl.ac.uk.

PMID: 24768341
DOI: 10.1016/j.jalz.2013.09.016

Abstract

Blood proteins and their complexes have become the focus of a great deal of interest in the context of their potential as biomarkers of Alzheimer's disease (AD). We used a SOMAscan assay for quantifying 1001 proteins in blood samples from 331 AD, 211 controls, and 149 mild cognitive impaired (MCI) subjects. The strongest associations of protein levels with AD outcomes were prostate-specific antigen complexed to α1-antichymotrypsin (AD diagnosis), pancreatic prohormone (AD diagnosis, left entorhinal cortex atrophy, and left hippocampus atrophy), clusterin (rate of cognitive decline), and fetuin B (left entorhinal atrophy). Multivariate analysis found that a subset of 13 proteins predicted AD with an accuracy of area under the curve of 0.70. Our replication of previous findings provides further evidence that levels of these proteins in plasma are truly associated with AD. The newly identified proteins could be potential biomarkers and are worthy of further investigation.

Keywords: Alzheimer's disease; Blood biomarkers; Proteins; Rate of progression; SOMAscan; sMRI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / blood*
Atrophy / etiology
Biomarkers / blood*
Blood Proteins / metabolism*
Brain / pathology
Cognitive Dysfunction / blood
Cohort Studies
Female
Humans
Logistic Models
Magnetic Resonance Imaging*
Male
Proteomics*
ROC Curve

Substances

Biomarkers
Blood Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding