Gender-related increase of tropomyosin-1 abundance in platelets of Alzheimer's disease and mild cognitive impairment patients

J Proteomics. 2018 Apr 30;178:73-81. doi: 10.1016/j.jprot.2017.12.018. Epub 2017 Dec 24.

Abstract

The incidence of Alzheimer's disease (AD) is higher in elderly women than in men. The molecular background of this gender-related risk, however, is largely unknown. In a previous proteomics study, we identified significantly elevated levels of monoamine oxidase-B and tropomyosin-1 in AD patients, together with significant changes of the genetic AD risk factors apolipoprotein E4 (APOE4) and glutathione S-transferase omega 1 (GSTO1), in platelets - a promising source for AD blood biomarkers. The present study aimed to investigate the gender-specificity as well as the disease-stage dependency of these biomarkers in AD patients and those with mild cognitive impairment (MCI). Tropomyosin-1 and monoamine oxidase-B protein levels were quantified by 2-D DIGE and 1-D Western blotting. Here, for the first time, we revealed a significant increase of 38&39kDa tropomyosin-1 protein levels in female but not male AD (+56%; p=0.008) and MCI patients (+46%; p=0.041) measured by 1-D WB. In contrast, levels of monoamine oxidase-B were, independently of gender, elevated in AD patients (+52%; p=0.009) but unaltered in MCI compared to control subjects. Moreover, we confirmed that APOE4-positive females are at a higher risk (OR=18.7; p=9.7E-09) of developing AD compared to APOE4-positive males (OR=6.5; p=5.9E-04). No gender-related effects were observed for GSTO1.

Significance: Platelet tropomyosin-1 constitutes a gender-related and stage-dependent protein in cognitive impairment. In contrast, platelet monoamine oxidase-B, frequently described to be increased in platelets and brains of AD patients, shows a gender-independent but stage-related increase since it is unaltered in MCI subjects. A blood biomarker test for this preceding stage of AD that considers gender-specificity is not yet available. The newly described AD-related platelet protein profiles might refine and facilitate routine diagnosis and enable early as well as tailored interventions.

Keywords: 2-D DIGE; Alzheimer's disease; Blood biomarker; Mild cognitive impairment; Monoamine oxidase-B; Tropomyosin-1.

MeSH terms

  • Alzheimer Disease / blood*
  • Apolipoprotein E4 / blood
  • Blood Platelets / chemistry
  • Blood Platelets / metabolism*
  • Cognitive Dysfunction / blood*
  • Female
  • Glutathione Transferase / blood
  • Humans
  • Male
  • Monoamine Oxidase / metabolism
  • Sex Factors
  • Tropomyosin / metabolism*

Substances

  • Apolipoprotein E4
  • TPM1 protein, human
  • Tropomyosin
  • Monoamine Oxidase
  • GSTO1 protein, human
  • Glutathione Transferase