The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease

Abstract

While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60+/-10 years, range 36-86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Abeta42/Abeta40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by epsilon4 genotype interactions were found for P-tau231 (beta=1.82; p<0.05) and IP (beta=1.6; p<0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in epsilon4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Abeta changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study.

Fig. 1

T-tau (A), P-tau231 (B), IP (C) concentrations and A β42/A β40 (D) in CSF as a function of age and ApoE genotype. Solid line: ε4 positive group; dashed line: ε4 negative group.

Fig. 2

Significant correlations between CSF variables: (A) correlation between IP and Ttau; (B) correlation between IP and P-tau 231; (C) correlation between T-tau and Aβ42/Afj40; (D) correlation between P-tau231 and Aβ40/Aβ42; (E) correlation between T-tau and P-tau231.