Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging

Abstract

CSF biomarkers and amyloid positron emission tomography reflect different aspects of Alzheimer's disease brain pathology, and therefore, less-than-perfect correspondence is expected. Automated assays are likely to increase the utility of CSF biomarkers.

Derivation of cutoffs for the Elecsys® amyloid β (1–42) assay in Alzheimer's disease

“…As an exception, the handling of Aβ (1–42) concentrations above the upper limit of the measuring range was included in rule defining CSF biomarker status: (1) if tau/Aβ (1–42) ratio was greater than the cutoff value and Aβ (1–42) ≤ 1700 pg/mL, CSF biomarker status was defined as positive and (2) if tau/Aβ (1–42) ratio was less than or equal to the cutoff or Aβ (1–42) > 1700 pg/mL, CSF biomarker status was defined as negative. It has been shown previously that this way of handling Aβ (1–42) values above the measuring range yields almost identical results for concordance with PET imaging as an analysis using Aβ (1–42) values estimated from the extrapolated calibration curve [18].…”

“…EXPEDITION and EXPEDITION2 were phase 3, double-blind, placebo-controlled international trials of solanezumab in patients aged 55-94 years with mild-tomoderate AD [7,8]. In both the trials, mild AD was defined as a Mini-Mental Status Examination (MMSE) score of 20-26, and moderate AD was defined as a MMSE score of [16][17][18][19]. Patients were required to provide written informed consent for the collection of CSF samples and data, and the studies were approved by the relevant institutional ethics committees and conducted in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki).…”

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

“…A potential limitation of the present study is that for 20% of our samples, the Elecsys measurements were above the upper limit of the measuring range at 1700 pg/mL, which was also reported in other studies [21,22]. For the present study, Aβ42 concentrations >1700 pg/mL were calculated by extrapolation of the calibration curve.…”

“…The Elecsys assays are reported to have very good intralaboratory and interlaboratory variations of 2% to 5% [7]. The Aβ42 CSF assay has been validated technically in artificial or quality control CSF (http://www.neurochem.gu.se/TheAlzAssQCprogram) [7,20], and clinically in research cohorts [21,22]. The Elecsys assays have not yet been tested in a real‐life setting, with a more diverse patient cohort and less standardized (pre)processing of samples compared with a research setting, that is, when CSF is collected in multiple, nonacademic memory clinics and sent to a central laboratory for biomarker analysis.…”

Spatial navigation ability predicts progression of dementia symptomatology

“…Values for Aβ 42 above 1700 pg/mL have not been validated and are not to be used in clinical decision making. The ratio between ptau 181 and Aβ 42 was used as the AD biomarker measure because it has been found to best map onto PET imaging results …”