Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jul 14;9(1):49.
doi: 10.1186/s13195-017-0275-5.

No added diagnostic value of non-phosphorylated tau fraction (p-taurel) in CSF as a biomarker for differential dementia diagnosis

Joery Goossens  1 , Maria Bjerke  1 , Hanne Struyfs  1 , Ellis Niemantsverdriet  1 , Charisse Somers  1 , Tobi Van den Bossche  2   3   4   5 , Sara Van Mossevelde  2   3   4   5 , Bart De Vil  6   7 , Anne Sieben  2   8 , Jean-Jacques Martin  8 , Patrick Cras  5   6   7 , Johan Goeman  4 , Peter Paul De Deyn  1   4   8 , Christine Van Broeckhoven  2   3 , Julie van der Zee  2   3 , Sebastiaan Engelborghs  9   10
Affiliations

No added diagnostic value of non-phosphorylated tau fraction (p-taurel) in CSF as a biomarker for differential dementia diagnosis

Joery Goossens et al. Alzheimers Res Ther. .

Abstract

Background: The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ1-42, t-tau, and p-tau181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-taurel), may improve differential dementia diagnosis. The goal of this study is to investigate if p-taurel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis.

Methods: The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ1-42, t-tau, p-tau181, and p-taurel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests.

Results: The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-taurel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-taurel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-taurel when differentiating between AD or non-AD dementias and controls.

Conclusions: The addition of p-taurel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.

Keywords: Alzheimer’s disease; Biomarkers; Cerebrospinal fluid; Creutzfeldt-Jakob disease; Dementia with Lewy bodies; Differential diagnosis; Frontotemporal lobar degeneration; Tau.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Epitopes of different tau assays. Binding sites of antibodies making up total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau 181), and non-phosphorylated tau fraction (p-tau rel ) assays. Binding of antibody AT270 requires phosphorylation of threonine (T), while binding of antibody 1G2 requires threonine (T) to be not phosphorylated
Fig. 2
Fig. 2
Dot plots of individual markers and ratios. Dot plots showing individual biomarker levels in each subgroup. a amyloid-beta of 42 amino acids (Aβ 1–42); b total tau protein (t-tau); c tau protein phosphorylated at threonine 181(p-tau 181); d non-phosphorylated tau fraction (p-tau rel); e Aβ1–42/t-tau; f Aβ1–42/p-tau181; g Aβ1–42/p-taurel; h p-tau181/t-tau; i p-tau181/p-taurel. Lines indicate median with interquartile range. AD Alzheimer’s disease, CJD Creutzfeldt-Jakob disease, DLB dementia with Lewy bodies, FTLD frontotemporal lobar degeneration
See this image and copyright information in PMC

References

    1. Somers C, Struyfs H, Goossens J, Niemantsverdriet E, Luyckx J, De Roeck N, De Roeck E, De Vil B, Cras P, Martin J-J, De Deyn P-P, Bjerke M, Engelborghs S. A decade of cerebrospinal fluid biomarkers for Alzheimer’s disease in Belgium. J Alzheimers Dis. 2016;54:383–95. doi: 10.3233/JAD-151097. - DOI - PubMed
    1. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S, Crutch S, Engelborghs S, Frisoni GB, Fox NC, Galasko D, Habert M-O, Jicha GA, Nordberg A, Pasquier F, Rabinovici G, Robert P, Rowe C, Salloway S, Sarazin M, Epelbaum S, de Souza LC, Vellas B, Visser PJ, Schneider L, et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol. 2014;13:614–29. doi: 10.1016/S1474-4422(14)70090-0. - DOI - PubMed
    1. Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol. 2010;6:131–44. doi: 10.1038/nrneurol.2010.4. - DOI - PubMed
    1. Blennow K, Hampel H: CSF markers for incipient Alzheimer’s disease. Lancet Neurol. 2003;2:605–13. - PubMed
    1. Braak H, Braak E. Frequency of stages of Alzheimer-related lesions in different age categories. Neurobiol Aging. 1997;18:351–7. doi: 10.1016/S0197-4580(97)00056-0. - DOI - PubMed