Plasma proteins predict conversion to dementia from prodromal disease

Abdul Hye; Joanna Riddoch-Contreras; Alison L Baird; Nicholas J Ashton; Chantal Bazenet; Rufina Leung; Eric Westman; Andrew Simmons; Richard Dobson; Martina Sattlecker; Michelle Lupton; Katie Lunnon; Aoife Keohane; Malcolm Ward; Ian Pike; Hans Dieter Zucht; Danielle Pepin; Wei Zheng; Alan Tunnicliffe; Jill Richardson; Serge Gauthier; Hilkka Soininen; Iwona Kłoszewska; Patrizia Mecocci; Magda Tsolaki; Bruno Vellas; Simon Lovestone

doi:10.1016/j.jalz.2014.05.1749

Plasma proteins predict conversion to dementia from prodromal disease

Alzheimers Dement. 2014 Nov;10(6):799-807.e2. doi: 10.1016/j.jalz.2014.05.1749. Epub 2014 Jul 8.

Authors

Abdul Hye¹, Joanna Riddoch-Contreras¹, Alison L Baird¹, Nicholas J Ashton¹, Chantal Bazenet¹, Rufina Leung¹, Eric Westman², Andrew Simmons¹, Richard Dobson¹, Martina Sattlecker¹, Michelle Lupton³, Katie Lunnon⁴, Aoife Keohane¹, Malcolm Ward⁵, Ian Pike⁵, Hans Dieter Zucht⁵, Danielle Pepin⁶, Wei Zheng⁶, Alan Tunnicliffe⁶, Jill Richardson⁷, Serge Gauthier⁸, Hilkka Soininen⁹, Iwona Kłoszewska¹⁰, Patrizia Mecocci¹¹, Magda Tsolaki¹², Bruno Vellas¹³, Simon Lovestone¹⁴

Affiliations

¹ Institute of Psychiatry, Department of Old Age Psychiatry, King's College London, London, UK.
² Institute of Psychiatry, Department of Old Age Psychiatry, King's College London, London, UK; Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
³ Institute of Psychiatry, Department of Old Age Psychiatry, King's College London, London, UK; Department of Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁴ University of Exeter Medical School, Exeter University, Exeter, UK.
⁵ Proteome Sciences plc, Research & Development, Proteome Sciences plc, Cobham, UK.
⁶ Protein Analysis and Detection, EMD Millipore Corporation, St. Charles, MO, USA.
⁷ Neurosciences Therapy Area Unit, GlaxoSmithKline Medicines Research Centre, Hertfordshire, UK.
⁸ Departments of Neurology & Neurosurgery, Psychiatry, Medicine, McGill Centre for Studies in Aging, Verdun, Canada; on behalf of GenADA consortium.
⁹ Department of Neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
¹⁰ Department of Old Age Psychiatry and Psychotic disorders, Medical University of Lodz, Lodz, Poland.
¹¹ Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
¹² 3rd Department of Neurology, Aristotle University, Thessaloniki, Greece.
¹³ Department of Internal Medicine and Geriatric Medicine, INSERM U 558, University of Toulouse, Toulouse, France.
¹⁴ Institute of Psychiatry, Department of Old Age Psychiatry, King's College London, London, UK; Department of Psychiatry, University of Oxford, Oxford, UK; on behalf of AddNeuroMed consortium. Electronic address: simon.lovestone@psych.ox.ac.uk.

Abstract

Background: The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia.

Methods: Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays.

Results: Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%).

Conclusions: We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints.

Keywords: Alzheimer's disease; Biomarker; Mild cognitive impairment; Pathology; Plasma; Prediction and magnetic resonance imaging.

Publication types

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

MeSH terms

Aged
Aged, 80 and over
Apolipoproteins E / genetics
Blood Proteins / metabolism*
Cognitive Dysfunction / blood
Cognitive Dysfunction / diagnosis
Cohort Studies
Dementia / blood*
Dementia / diagnosis*
Disease Progression
Female
Humans
Immunoassay
Magnetic Resonance Imaging
Male
Mental Status Schedule
Predictive Value of Tests
Prodromal Symptoms*
ROC Curve
Statistics as Topic

Substances

Apolipoproteins E
Blood Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding