The clinical use of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's Biomarkers Standardization Initiative

Alzheimers Dement. 2014 Nov;10(6):808-17. doi: 10.1016/j.jalz.2014.03.003. Epub 2014 Aug 20.

Abstract

Background: Cerebrospinal fluid (CSF) biomarkers β-amyloid 1-42 (Aβ1-42), also expressed as Aβ1-42:Aβ1-40 ratio, T-tau, and P-tau181P, have proven diagnostic accuracy for mild cognitive impairment and Alzheimer's disease (AD). How to use, interpret, and disclose biomarker results drives the need for standardization.

Methods: Previous Alzheimer's Biomarkers Standardization Initiative meetings discussed preanalytical issues affecting Aβ1-42 and tau in CSF. This second round of consensus meetings focused on issues related to clinical use of AD CSF biomarkers.

Results: Consensus was reached that lumbar puncture for AD CSF biomarker analysis be considered as a routine clinical test in patients with early-onset dementia, at the prodromal stage or with atypical AD. Moreover, consensus was reached on which biomarkers to use, how results should be interpreted, and potential confounding factors.

Conclusions: Changes in Aβ1-42, T-tau, and P-tau181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up.

Keywords: Alzheimer's disease; Amyloid-β peptides; Biomarkers; Cerebrospinal fluid; Standardization; Tau.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biomarkers / cerebrospinal fluid*
  • Cognitive Dysfunction / cerebrospinal fluid
  • Cognitive Dysfunction / diagnosis
  • Consensus
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Peptide Fragments / cerebrospinal fluid
  • Reference Standards*
  • tau Proteins / cerebrospinal fluid

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • tau Proteins