Differential Diagnosis of Dementia with High Levels of Cerebrospinal Fluid Tau Protein

J Alzheimers Dis. 2016;51(3):905-13. doi: 10.3233/JAD-151111.


Background: Total Tau concentration in cerebrospinal fluid (CSF) is widely used as a biomarker in the diagnosis of neurodegenerative process primarily in Alzheimer's disease (AD). A particularly high Tau level may indicate AD but may also be associated with Creutzfeldt-Jakob disease (CJD). In such situations little is known about the distribution of differential diagnoses.

Objective: Our study aimed to describe the different diagnoses encountered in clinical practice for patients with dementia and CSF Tau levels over 1000 pg/ml. We studied the p-Tau/Tau ratio to specify its ability to distinguish AD from CJD.

Methods: Patients (n = 202) with CSF Tau levels over 1000 pg/ml were recruited in three memory clinics in France. All diagnoses were made using the same diagnostic procedure and criteria.

Results: Patients were diagnosed with AD (n = 148, 73.2%), mixed dementia (n = 38, 18.8%), CJD, vascular dementia (n = 4, 2.0% for each), Lewy body dementia, and frontotemporal dementia (n = 3, 1.5% for each). Dispersion of CSF Tau levels clearly showed an overlap between all diagnoses. Using the p-Tau/Tau ratio suggestive of CJD (<0.075), all CJD patients were correctly categorized and only two AD patients were miscategorized. This ratio was highly associated with CJD compared to AD (p < 0.0001).

Conclusion: Our study showed that in clinical practice, extremely high CSF Tau levels are mainly related to diagnosis of AD. CJD patients represent a minority. Our results support a sequential interpretation algorithm for CSF biomarkers in dementia. High CSF Tau levels should alert clinicians to check the p-Tau/Tau ratio to consider a probable diagnosis of CJD.

Keywords: Alzheimer’s disease; Creutzfeldt-Jakob disease; cerebrospinal fluid biomarker; dementia; tau.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Creutzfeldt-Jakob Syndrome / cerebrospinal fluid*
  • Dementia, Vascular / cerebrospinal fluid
  • Diagnosis, Differential
  • Female
  • France
  • Frontotemporal Dementia / cerebrospinal fluid
  • Humans
  • Lewy Body Disease / cerebrospinal fluid
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Phosphorylation
  • Retrospective Studies
  • Sex Factors
  • tau Proteins / cerebrospinal fluid*


  • Biomarkers
  • MAPT protein, human
  • tau Proteins