Evaluation of cerebrospinal fluid phosphorylated tau 231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia

CNS Neurosci Ther. 2018 Aug;24(8):734-740. doi: 10.1111/cns.12814. Epub 2018 Feb 17.


Background: The diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) is still largely based on clinical guidelines and exclusion of other diseases that may lead to dementia.

Aims: In this study, we assessed whether the use of sensitive and specific biomarkers such as phosphorylated tau proteins could contribute to an earlier and more accurate diagnosis of AD and VaD, as well as to their differentiation.

Material and methods: A total of 198 patients, of which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the analyses. We analyzed cerebrospinal fluid (CSF) levels of total tau protein (t-tau), tau protein phosphorylated at threonine 231 (p-tau231), and factor score (FS) determined by combination of p-tau231 and Mini-Mental State Examination (MMSE) in patients with AD and VaD, as well as in HC. We tested the diagnostic accuracy of these biomarkers in the CSF and FS (p-tau231, MMSE) in differentiating AD from VaD and HC.

Results: Total tau levels were significantly elevated in subjects with AD compared to HC, as well as in VaD subjects compared to HC.

Discussion: p-tau231 levels were significantly higher in patients with ADvsHC as well in patients with VaD vsHC. p-tau231 levels did not distinguish AD from VaD patients. Importantly, FS(p-tau231 and MMSE) showed statistically significant differences in the distribution of subjects with AD and VaD.

Conclusion: These results indicate that FS (p-tau231 and MMSE) has a strong potential to provide an early distinction between AD and VaD.

Keywords: Alzheimer's disease; biomarkers; cerebrospinal fluid; tau proteins; vascular dementia.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / diagnosis*
  • Biomarkers / cerebrospinal fluid*
  • Dementia, Vascular / cerebrospinal fluid*
  • Diagnosis, Differential*
  • Female
  • Humans
  • Male
  • Mental Status and Dementia Tests
  • Middle Aged
  • Phosphorylation
  • ROC Curve
  • Retrospective Studies
  • Statistics, Nonparametric
  • tau Proteins / cerebrospinal fluid*


  • Biomarkers
  • tau Proteins