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

TY - JOUR

T1 - Plasma protein biomarkers of Alzheimer’s disease endophenotypes in asymptomatic older twins

T2 - early cognitive decline and regional brain volumes

AU - Kiddle, S J

AU - Steves, C J

AU - Mehta, M

AU - Simmons, A

AU - Xu, X

AU - Newhouse, S

AU - Sattlecker, M

AU - Ashton, Nicholas

AU - Bazenet, C

AU - Killick, Richard

AU - Adnan, J

AU - Westman, E

AU - Nelson, S

AU - Soininen, H

AU - Kloszewska, I

AU - Mecocci, P

AU - Tsolaki, M

AU - Vellas, B

AU - Curtis, C

AU - Breen, G

AU - Williams, S C R

AU - Lovestone, S

AU - Spector, T D

AU - Dobson, R J B

PY - 2015/6

Y1 - 2015/6

N2 - 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.

AB - 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.

U2 - 10.1038/tp.2015.78

DO - 10.1038/tp.2015.78

M3 - Article

SN - 2158-3188

VL - 5

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 6

M1 - e584

ER -