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

Abstract Background Low amyloid β 42 (Aβ 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 Aβ 42 , total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. Methods CSF Aβ 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 ɛ4 carriers and noncarriers. Results The median levels of all markers were significantly different between young ( 42 : P = .03; tau: P = .02; p-tau: P = .002; tau/Aβ 42 : P = .004; p-tau/Aβ 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/Aβ 42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P = .002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aβ 42 concentrations. Conclusion In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aβ 42 low levels represent a preclinical AD biomarker.