Clinical application of plasma P-tau217 to assess eligibility for amyloid-lowering immunotherapy in memory clinic patients with early Alzheimer’s disease

Autor: Matthew D. Howe, Karysa J. Britton, Hannah E. Joyce, William Menard, Sheina Emrani, Zachary J. Kunicki, Melanie A. Faust, Brittany C. Dawson, Meghan C. Riddle, Edward D. Huey, Shorena Janelidze, Oskar Hansson, Stephen P. Salloway
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Alzheimer’s Research & Therapy, Vol 16, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 1758-9193
DOI: 10.1186/s13195-024-01521-9
Popis: Abstract Background With the approval of disease-modifying treatments (DMTs) for early Alzheimer’s disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-β (Aβ) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP). Methods In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific and BioFINDER-2 training data, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aβ-PET/CSF testing as the standard of truth. Results Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aβ-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aβ positivity in potential DMT candidates (AUC = 0.97 [0.92–1]), with diagnostic accuracy ranging from 0.88 (0.76–0.95, p = 0.028) to 0.96 (0.86–1, p
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