Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort

Neurology. 2012 Jan 3;78(1):47-54. doi: 10.1212/WNL.0b013e31823ed0f0. Epub 2011 Dec 14.


Objective: To determine how amyloid β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia.

Methods: Baseline CSF was collected from 512 patients with Alzheimer disease (AD) and 272 patients with other types of dementia (OD), 135 patients with a psychiatric disorder (PSY), and 275 patients with subjective memory complaints (SMC). Aβ42, t-tau, and p-tau (at amino acid 181) were measured in CSF by ELISA. Autopsy was obtained in a subgroup of 17 patients.

Results: A correct classification of patients with AD (92%) and patients with OD (66%) was accomplished when CSF Aβ42 and p-tau were combined. Patients with progressive supranuclear palsy had normal CSF biomarker values in 90%. Patients with Creutzfeldt-Jakob disease demonstrated an extremely high CSF t-tau at a relatively normal CSF p-tau. CSF AD biomarker profile was seen in 47% of patients with dementia with Lewy bodies (DLB), 38% in corticobasal degeneration (CBD), and almost 30% in frontotemporal lobar degeneration (FTLD) and vascular dementia (VaD). PSY and SMC patients had normal CSF biomarkers in 91% and 88%. Older patients are more likely to have a CSF AD profile. Concordance between clinical and neuropathologic diagnosis was 85%. CSF markers reflected neuropathology in 94%.

Conclusion: CSF Aβ42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future.

MeSH terms

  • Age Factors
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Cohort Studies
  • Dementia / cerebrospinal fluid*
  • Dementia / diagnosis
  • Diagnosis, Differential
  • Female
  • Humans
  • Male
  • Memory*
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Predictive Value of Tests
  • tau Proteins / cerebrospinal fluid*


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