Cerebrospinal fluid markers for Alzheimer's disease in a cognitively healthy cohort of young and old adults

Background: Low amyloid beta(42) (A beta(42)) and high total tau and phosphorylated tau (p-tau) concentrations in the cerebrospinal fluid (CSF) are biomarkers of Alzheimer's disease (AD), reflecting brain deposition of amyloid plaques and tangles. Age and apolipoprotein E allele E4 are two strong risk factors for AD, but few data are still available on their effect on CSF markers in normal aging. Objective: To study the effect of age on CSF A beta(42), total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. Methods: CSF A beta(42) levels of 81 subjects (27% female, 53 +/- 15.3 years, range: 21-88) were determined with sandwich enzyme-linked immunosorbent assay; of these, total tau and p-tau levels were measured in 61 (75%) and 42 (52%) cases, respectively. A linear regression analysis between age and CSF markers was carried out on the whole sample and separately in apolipoprotein E allele epsilon 4 carriers and noncarriers. Results: The median levels of all markers were significantly different between young (<65 years) and old (>= 65 years) subjects (A beta(42): P = .03; tau: P = .02; p-tau: P = .002; tau/A beta(42): P = .004; p-tau/A beta(42): P = .03). The association of marker levels with age was confirmed in linear regression models, where a positive relationship with age was observed for total tau (B = 2.3; 95% confidence interval [CI]: 0.89 to 3.7; P = .002), p-tau (B = 0.5; 95% CI: 0.1 to 0.9; P = .02), and tau/A beta(42) ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF A beta(42) concentrations. Conclusion: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether A beta(42) low levels represent a preclinical AD biomarker. (C) 2012 The Alzheimer's Association. All rights reserved.