Alzheimer's disease biomarker discovery using SOMAscan multiplexed protein technology.
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.
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.
Martina
M
Sattlecker
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.
Steven J
SJ
Kiddle
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.
Stephen
S
Newhouse
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.
Petroula
P
Proitsi
SomaLogic, Boulder, CO, USA.
Sally
S
Nelson
SomaLogic, Boulder, CO, USA.
Stephen
S
Williams
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.
Caroline
C
Johnston
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.
Richard
R
Killick
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.
Andrew
A
Simmons
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.
Eric
E
Westman
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.
Angela
A
Hodges
Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Hilkka
H
Soininen
Medical University of Lodz, Lodz, Poland.
Iwona
I
Kłoszewska
Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
Patrizia
P
Mecocci
3rd Department of Neurology, Aristotle University, Thessaloniki, Greece.
Magda
M
Tsolaki
INSERM U 558, University of Toulouse, Toulouse, France.
Bruno
B
Vellas
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.
Simon
S
Lovestone
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.
Richard J B
RJ
Dobson
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D001284:Atrophy / Q000209:etiology; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D060825:Cognitive Dysfunction / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D040901:Proteomics; D012372:ROC Curve
D015415:Biomarkers; D001798:Blood Proteins
Alzheimer's disease; Blood biomarkers; Proteins; Rate of progression; SOMAscan; sMRI