Plasma Protein Biomarkers of Alzheimer's Disease Endophenotypes in Asymptomatic Older Twins: Early Cognitive Decline and Regional Brain Volumes

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2015 Jun 17

PMID 26080319

Citations 23

Authors

S J Kiddle

C J Steves

M Mehta

A Simmons

X Xu

S Newhouse

M Sattlecker

N J 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

Affiliations

Soon will be listed here.

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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