Cerebrospinal fluid biomarkers for Alzheimer's and vascular disease vary by age, gender, and APOE genotype in cognitively normal adults

Alzheimers Res Ther. 2017 Jul 3;9(1):48. doi: 10.1186/s13195-017-0271-9.

Abstract

Background: This study sought to evaluate gender and APOE genotype-related differences in the concentrations of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and cerebrovascular injury across the life span of cognitively normal adults.

Methods: CSF amyloid beta1-42 (Aβ42), phospho-tau-181 (p-tau181), and total tau were measured in 331 participants who were between the ages of 21 and 100. CSF E-selectin and vascular cell adhesion protein 1 (VCAM1) were measured in 249 participants who were between the ages of 50 and 100.

Results: CSF total tau and p-tau181 increased with age over the adult life span (p < 0.01) with no gender differences in those increases. CSF Aβ42 concentration varied according to age, gender, and APOE genotype (interaction of age × gender × ε4, p = 0.047). CSF VCAM1, but not E-selectin, increased with age (p < 0.01), but both were elevated in men compared to women (p < 0.01).

Conclusions: Female APOE-ε4 carriers appear at higher risk for AD after age 50. In contrast, men may experience a relatively higher rate of cerebrovascular injury in middle and early old age.

Keywords: APOE genotype; Age; Alzheimer’s disease; Biomarkers; Cerebrospinal fluid; Cerebrovascular disease; Gender.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / cerebrospinal fluid
  • Aging / genetics
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Apolipoprotein E4 / genetics
  • Biomarkers / cerebrospinal fluid*
  • E-Selectin / metabolism
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Sex Characteristics*
  • Vascular Cell Adhesion Molecule-1 / cerebrospinal fluid
  • Vascular Diseases / cerebrospinal fluid*
  • Vascular Diseases / genetics*
  • Young Adult
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Biomarkers
  • E-Selectin
  • Peptide Fragments
  • Vascular Cell Adhesion Molecule-1
  • amyloid beta-protein (1-42)
  • tau Proteins