Karikari TK, Emeršič A, Vrillon A, Lantero-Rodriguez J, Ashton NJ, Kramberger MG, Dumurgier J, Hourregue C, Čučnik S, Brinkmalm G, Rot U, Zetterberg H, Paquet C, Blennow K. Head-to-head comparison of clinical performance of CSF phospho-tau T181 and T217 biomarkers for Alzheimer's disease diagnosis. Alzheimers Dement. 2021 May;17(5):755-767. Epub 2020 Nov 30 PubMed. Correction.
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Axon Neuroscience
This paper nicely compares pT217 and pT181 tau levels in CSF of controls, MCI and AD patients. Almost no difference between N-p-tau217 and N-p-tau181 assays was found in a back-to-back comparison. The authors found a weaker diagnostic accuracy of mid-p-tau181 than both N-terminal-ptau assays. It will be interesting to include also the mid-p-tau217 assay for that comparison.
Recently, we developed such a mid-p-tau217 assay (Hanes et al., 2020), and we showed better diagnostic accuracy than did the mid-p-tau181 assay. Whether our mid-p-tau217 assay can show similar or better diagnostic accuracy than N-p-tau217 and N-p-tau181 assays has to be analyzed.
However, I find it mysterious that the authors used as controls only unimpaired individuals who are Aβ42-negative. Why were unimpaired individuals with decreased Aβ42 not included, even though the authors mention in the introduction that about 30 percent of healthy people have decreased Aβ42? I also recently observed such a trend—to not to use Aβ42-positive controls—at some conferences. If the assay's diagnostic performance is to be complete, then unimpaired individuals with decreased Aβ42 should be included.
References:
Hanes J, Kovac A, Kvartsberg H, Kontsekova E, Fialova L, Katina S, Kovacech B, Stevens E, Hort J, Vyhnalek M, Boonkamp L, Novak M, Zetterberg H, Hansson O, Scheltens P, Blennow K, Teunissen CE, Zilka N. Evaluation of a novel immunoassay to detect p-tau Thr217 in the CSF to distinguish Alzheimer disease from other dementias. Neurology. 2020 Dec 1;95(22):e3026-e3035. Epub 2020 Sep 24 PubMed.
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