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

Donata Paternicò, Samantha Galluzzi, Valeria Drago, Luisella Bocchio-Chiavetto, Roberta Zanardini, Laura Pedrini, Manuela Baronio, Giovanni Amicucci, Giovanni B. Frisoni

Research output: Contribution to journalArticlepeer-review


Background: Low amyloid β42 (Aβ42) 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 Aβ42, total tau, and p-tau levels in a well-characterized group of cognitively normal subjects. Methods: CSF Aβ42 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 ε4 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/Aβ42: 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/Aβ42 ratio (B = 0.006; 95% CI: 0.002 to 0.01; P =.002). No subjects showed abnormal tau, whereas 19% showed abnormal CSF Aβ42 concentrations. Conclusion: In cognitively normal subjects, the concentrations of CSF biomarkers of AD are associated with age. Further longitudinal studies could clarify whether Aβ42 low levels represent a preclinical AD biomarker.

Original languageEnglish
Pages (from-to)520-527
Number of pages8
JournalAlzheimer's and Dementia
Issue number6
Publication statusPublished - Nov 2012


  • Age
  • Alzheimer's disease
  • Apolipoprotein E
  • Biomarkers
  • Cerebrospinal fluid
  • Healthy adult

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology


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