Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays

Alzheimers Dement. 2023 May;19(5):1913-1924. doi: 10.1002/alz.12841. Epub 2022 Nov 12.

Abstract

Introduction: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences.

Methods: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio.

Results: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94).

Discussion: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD.

Highlights: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.

Keywords: biomarker; dementia; disease; phosphorylated tau; plasma; tau.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / cerebrospinal fluid
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction* / blood
  • Cognitive Dysfunction* / cerebrospinal fluid
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoassay*
  • tau Proteins* / blood
  • tau Proteins* / cerebrospinal fluid
  • tau Proteins* / metabolism

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • tau Proteins