Reproducibility of Alzheimer's Disease Cerebrospinal Fluid-Biomarker Measurements under Clinical Routine Conditions

摘要

Analysis of cerebrospinal fluid (CSF) is one of the key tools for the state-of-the-art differential diagnosis of dementias. Dementia due to Alzheimer's disease (AD) is characterized by elevated CSF levels of total Tau (tTau) and phospho-181-Tau (pTau) and low CSF amyloid-beta(42) (A beta(42)). Discrepancies in the laboratory analysis of human materials are well known and much effort has been put into harmonization procedures. In this study, we measured CSF biomarkers of more than 100 patients obtained under clinical routine conditions in two different clinical laboratories. The CSF biomarker levels obtained from the two different sites were significantly correlated: R-2 = 0.7129 (tTau, p 0.001), 0.7914 (pTau, p 0.001), 0.5078 (A beta(42), p 0.001), 0.5739 (A beta(40), p 0.001), and 0.4308 (A beta(42/40), p 0.001). However, the diagnostic classifications of the A beta(42), tTau, and pTau levels of identical subjects into normal versus pathological range made by the two different sites showed substantial discrepancies (31.5%, 29.6%, and 25.0% discordant cases, respectively). Applying A beta(42/40), instead of CSF A beta(42) alone, lead to a reduction of the discordant cases to 16.8%. Our findings suggest that CSF A beta(42/40) can outperform A beta(42) as a biomarker for AD neuropathology, not only under well-controlled study conditions but also in real life clinical routine. Thus, we recommend the inclusion of A beta(42/40) as a CSF biomarker in the diagnostic procedure.