Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment
Abstract Objectives We sought to compare two of the most promising plasma biomarkers for Alzheimer disease (AD): pTau181 and pTau217.Methods pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well characterized prospective multicentre BALTAZAR cohort of mild cognitive impairment (MCI) participants.Results Among MCI participants, 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 hazard ratios of 1.38 (1.26-1.51) for pTau181 compared to 8.22 (5.45-12.39) for pTau217. The AUC for predicting Aβ+ was 0.783 (95%CI: 0.721-0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95%CI: 0.868-0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex, and 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 MMSE were −2.32 versus −0.65.Conclusions Plasma pTau217 and pTau181 both correlate with AD, but the fold-change in pTau217 make it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 07. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lehmann, Sylvain [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2024.01.21.24301570 |
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| PPN (Katalog-ID): |
XBI042245583 |
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| 520 | |a Abstract Objectives We sought to compare two of the most promising plasma biomarkers for Alzheimer disease (AD): pTau181 and pTau217.Methods pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well characterized prospective multicentre BALTAZAR cohort of mild cognitive impairment (MCI) participants.Results Among MCI participants, 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 hazard ratios of 1.38 (1.26-1.51) for pTau181 compared to 8.22 (5.45-12.39) for pTau217. The AUC for predicting Aβ+ was 0.783 (95%CI: 0.721-0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95%CI: 0.868-0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex, and 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 MMSE were −2.32 versus −0.65.Conclusions Plasma pTau217 and pTau181 both correlate with AD, but the fold-change in pTau217 make it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Schraen-Maschke, Susanna |4 aut | |
| 700 | 1 | |a Vidal, Jean-Sébastien |4 aut | |
| 700 | 1 | |a Delaby, Constance |0 (orcid)0000-0002-8606-6814 |4 aut | |
| 700 | 1 | |a Buée, Luc |4 aut | |
| 700 | 1 | |a Blanc, Frédéric |0 (orcid)0000-0002-6714-3247 |4 aut | |
| 700 | 1 | |a Paquet, Claire |0 (orcid)0000-0002-2273-7316 |4 aut | |
| 700 | 1 | |a Allinquant, Bernadette |4 aut | |
| 700 | 1 | |a Bombois, Stéphanie |4 aut | |
| 700 | 1 | |a Gabelle, Audrey |4 aut | |
| 700 | 1 | |a Hanon, Olivier |4 aut | |
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