• Sylvain Lehmann, Susanna Schraen-Maschke, Jean-Sébastien Vidal, Constance Delaby, Luc Buee, Frédéric Blanc, Claire Paquet, Bernadette Allinquant, Stéphanie Bombois, Audrey Gabelle, Olivier Hanon, and BALTAZAR study group.
• LBPC-PPC, Université de Montpellier, INM INSERM, IRMB CHU de Montpellier, Montpellier, France sylvain.lehmann@umontpellier.fr.
• J. Neurol. Neurosurg. Psychiatr. 2024 Oct 16; 95 (11): 104610531046-1053.

BackgroundAmong plasma biomarkers for Alzheimer's disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors.MethodpTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well-characterised prospective multicentre BALTAZAR (Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk) cohort of participants with mild cognitive impairment (MCI).ResultsAmong participants with MCI, 55% were Aβ+ and 29% developed dementia due to AD. pTau181 and pTau217 were higher in the Aβ+ population with fold change of 1.5 and 2.7, respectively. MCI that converted to AD also had higher levels than non-converters, with HRs of 1.38 (1.26 to 1.51) for pTau181 compared with 8.22 (5.45 to 12.39) for pTau217. The area under the curve for predicting Aβ+ was 0.783 (95% CI 0.721 to 0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95% CI 0.868 to 0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex and apolipoprotein E ε4 (APOEε4) status, in a logistic model. Age, APOEε4 and renal dysfunction were associated with pTau levels, but the clinical performance of pTau217 was only marginally altered by these factors. Using a two cut-point approach, a 95% positive predictive value for Aβ+ corresponded to pTau217 >0.8 pg/mL and a 95% negative predictive value at <0.23 pg/mL. At these two cut-points, the percentages of MCI conversion were 56.8% and 9.7%, respectively, while the annual rates of decline in Mini-Mental State Examination were -2.32 versus -0.65.ConclusionsPlasma pTau217 and pTau181 both correlate with AD, but the fold change in pTau217 makes it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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