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

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S J Kiddle ; C J Steves ; M Mehta ; A Simmons ; X Xu ; S Newhouse ; M Sattlecker ; Nicholas Ashton ; C Bazenet ; R Killick ; J Adnan ; E Westman ; S Nelson ; H Soininen ; I Kloszewska ; P Mecocci ; M Tsolaki ; B Vellas ; C Curtis ; G Breen ; S C R Williams ; S Lovestone ; T D Spector ; R J B Dobson

Original languageEnglish
Article numbere584
Number of pages6
JournalTranslational psychiatry
Volume5
Issue number6
DOIs
StatePublished - 16 Jun 2015

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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.

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