Comparison of cerebrospinal fluid levels of tau and Aβ 1-42 in Alzheimer disease and frontotemporal degeneration using 2 analytical platforms

  • Irwin D
  • McMillan C
  • Toledo J
 et al. 
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Abstract

OBJECTIVE: To use values of cerebrospinal fluid tau and β-amyloid obtained from 2 different analytical immunoassays to differentiate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD).

DESIGN: Cerebrospinal fluid values of total tau (T-tau) and β-amyloid 1-42 (Aβ 1-42) obtained using the Innotest enzyme-linked immunosorbent assay were transformed using a linear regression model to equivalent values obtained using the INNO-BIA AlzBio3 (xMAP; Luminex) assay. Cutoff values obtained from the xMAP assay were developed in a series of autopsy-confirmed cases and cross validated in another series of autopsy-confirmed samples using transformed enzyme-linked immunosorbent assay values to assess sensitivity and specificity for differentiating AD from FTLD.

SETTING: Tertiary memory disorder clinics and neuropathologic and biomarker core centers.

PARTICIPANTS: Seventy-five samples from patients with cerebrospinal fluid data obtained from both assays were used for transformation of enzyme-linked immunosorbent assay values. Forty autopsy-confirmed cases (30 with AD and 10 with FTLD) were used to establish diagnostic cutoff values and then cross validated in a second sample set of 21 autopsy-confirmed cases (11 with AD and 10 with FTLD) with transformed enzyme-linked immunosorbent assay values.

MAIN OUTCOME MEASURE: Diagnostic accuracy using transformed biomarker values.

RESULTS: Data obtained from both assays were highly correlated. The T-tau to Aβ 1-42 ratio had the highest correlation between measures (r = 0.928, P < .001) and high reliability of transformation (intraclass correlation coefficient= 0.89). A cutoff of 0.34 for the T-tau to Aβ 1-42 ratio had 90% and 100% sensitivity and 96.7% and 91% specificity to differentiate FTLD cases in the validation and cross-validation samples, respectively.

CONCLUSIONS: Values from 2 analytical platforms can be transformed into equivalent units, which can distinguish AD from FTLD more accurately than the clinical diagnosis.

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Authors

  • David J. Irwin

  • Corey T. McMillan

  • Steven E. Arnold

  • Leslie M. Shaw

  • Li San Wang

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