CSF biomarkers for the differential diagnosis of Alzheimer's disease: A large-scale international multicenter study

Alzheimers Dement. 2015 Nov;11(11):1306-15. doi: 10.1016/j.jalz.2014.12.006. Epub 2015 Mar 21.


Introduction: The aim of this study was to test the diagnostic value of cerebrospinal fluid (CSF) beta-amyloid (Aβ1-42), phosphorylated tau, and total tau (tau) to discriminate Alzheimer's disease (AD) dementia from other forms of dementia.

Methods: A total of 675 CSF samples collected at eight memory clinics were obtained from healthy controls, AD dementia, subjective memory impairment, mild cognitive impairment, vascular dementia, Lewy body dementia (LBD), fronto-temporal dementia (FTD), depression, or other neurological diseases.

Results: CSF Aβ1-42 showed the best diagnostic accuracy among the CSF biomarkers. At a sensitivity of 85%, the specificity to differentiate AD dementia against other diagnoses ranged from 42% (for LBD, 95% confidence interval or CI = 32-62) to 77% (for FTD, 95% CI = 62-90).

Discussion: CSF Aβ1-42 discriminates AD dementia from FTD, but shows significant overlap with other non-AD forms of dementia, possibly reflecting the underlying mixed pathologies.

Keywords: Alzheimer's disease; Biomarker; CSF; Cerebrospinal fluid; Classification; Dementia; Differential diagnosis; Fronto-temporal dementia; Lewy body dementia; Vascular dementia.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis*
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Diagnosis, Differential
  • Female
  • Humans
  • Internationality
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Sensitivity and Specificity
  • Spinal Puncture
  • tau Proteins / cerebrospinal fluid*


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