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Transl Psychiatry. 2015 Jun 16;5:e584. doi: 10.1038/tp.2015.78.

Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes.

Author information

1
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
2
Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
3
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
4
1] Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
5
1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
6
1] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK [2] Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
7
Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
8
Department of Neurobiology, Care Sciences and Society, Karolinska Instituet, Stockholm, Sweden.
9
SomaLogic, Boulder, CO, USA.
10
1] Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland [2] NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
11
Department of Old Age Psychiatry and Psychotic disorders, Medical University of Łódź, Łódź, Poland.
12
Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
13
3rd Department of Neurology, Aristotle University, Thessaloniki, Greece.
14
Department of Internal Medicine and Geriatric Medicine, INSERM University of Toulouse, Toulouse, France.
15
Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK.

Abstract

There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general. Panel-based proteomics was performed using SOMAscan on plasma samples from TwinsUK subjects who are asymptomatic for AD, measuring the level of 1129 proteins. Protein levels were compared with 10-year change in CANTAB-paired associates learning (PAL; n = 195), and regional brain volumes (n = 34). Replication of proteins associated with regional brain volumes was performed in 254 individuals from the AddNeuroMed cohort. Across all the proteins measured, genetic factors were found to explain ~26% of the variability in blood protein levels on average. The plasma level of the mitogen-activated protein kinase (MAPK) MAPKAPK5 protein was found to positively associate with the 10-year change in CANTAB-PAL in both the individual and twin difference context. The plasma level of protein MAP2K4 was found to suggestively associate negatively (Q < 0.1) with the volume of the left entorhinal cortex. Future studies will be needed to assess the specificity of MAPKAPK5 and MAP2K4 to eventual conversion to AD.

PMID:
26080319
PMCID:
PMC4490288
DOI:
10.1038/tp.2015.78
[Indexed for MEDLINE]
Free PMC Article

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