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

Transl Psychiatry. 2015 Jun 16;5(6):e584. doi: 10.1038/tp.2015.78.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / pathology
  • Asymptomatic Diseases
  • Biomarkers / blood
  • Brain / pathology*
  • Endophenotypes*
  • Entorhinal Cortex / pathology
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / blood*
  • MAP Kinase Kinase 4 / blood*
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Organ Size
  • Protein-Serine-Threonine Kinases / blood*
  • Twins / genetics*
  • Twins / psychology

Substances

  • Biomarkers
  • Intracellular Signaling Peptides and Proteins
  • MAP-kinase-activated kinase 5
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase 4
  • MAP2K4 protein, human