Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231

Katharina Buerger, Raymond Zinkowski, Stefan J. Teipel, Tero Tapiola, Hiroyuki Arai, Kaj Blennow, Niels Andreasen, Klaus Hofmann-Kiefer, John DeBernardis, Daniel Kerkman, Cheryl McCulloch, Russell Kohnken, Frank Padberg, Tuula Pirttilä, Marc B. Schapiro, Stanley I. Rapoport, Hans Jürgen Möller, Peter Davies, Harald Hampel

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221 Citations (Scopus)


Background: Phosphorylation of tau protein at threonine 231 (using full-length tau, 441 amino acids, for the numbering scheme) (p-tau231) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). Objectives: To determine to what extent CSF levels of p-tau231 distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-tau231 levels are a better diagnostic marker than levels of total tau protein (t-tau) in CSF. Design and Setting: Cross-sectional, multicenter, memory clinic-based studies. Participants: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. Main Outcome Measures: Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays. Results: Mean CSF levels of p-tau231 were significantly elevated in the AD group compared with all other groups. Levels of p-tau231 did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-tau231 levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls (P=.03) and demented subjects (P<.001), particularly those with FTD (P<.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-tau231 compared with t-tau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. Conclusion: Increased levels of CSF p-tau231 may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.

Original languageEnglish
Pages (from-to)1267-1272
Number of pages6
JournalArchives of Neurology
Issue number8
Publication statusPublished - 2002

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


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