Abnormal hyperphosphorylation of the microtubule-associated protein
tau and its incorporation into neurofibrillary tangles are major hallmarks
of the pathogenesis of Alzheimer disease (AD). Different tau phosphoepitopes
can be sensitively detected in cerebrospinal fluid (CSF).
To compare the diagnostic accuracy of CSF concentrations of tau proteins
phosphorylated at 3 pathophysiologically important epitopes (p-tau) to discriminate
among patients with AD, nondemented control subjects, and patients with other
Design and Setting
Cross-sectional, bicenter, memory clinic–based studies.
One hundred sixty-one patients with a clinical diagnosis of AD, frontotemporal
dementia, dementia with Lewy bodies, or vascular dementia and 45 nondemented
controls (N = 206).
Main Outcome Measures
Levels of tau protein phosphorylated at threonine 231 (p-tau231), threonine 181 (p-tau181), and serine 199 (p-tau199). The CSF p-tau protein levels were measured using 3 different enzyme-linked
The mean CSF levels of the studied p-tau proteins were significantly
elevated in patients with AD compared with the other groups. Applied as single
markers, p-tau231and p-tau181 reached specificity levels
greater than 75% between AD and the combined non-AD group when sensitivity
was set at 85% or greater. Statistical differences between the assay performances
are presented. Particularly, discrimination between AD and dementia with Lewy
bodies was maximized using p-tau181at a sensitivity of 94% and
a specificity of 64%, and p-tau231 maximized group separation between
AD and frontotemporal dementia with a sensitivity of 88% and a specificity
of 92%. Combinations of the 3 markers did not add discriminative power compared
with the application as single markers.
The p-tau proteins in CSF come closest to fulfilling the criteria of
a biological marker of AD. There is a tendency for p-tau proteins to perform
differently in the discrimination of primary dementia disorders from AD.