Comparison of Plasma p-tau217 and [¹⁸F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia.

Abstract

To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [¹⁸F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments. We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [¹⁸F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications. To determine whether the [¹⁸F]FDG-PET images were compatible with AD, images were visually rated by 2 nuclear medicine experts. Using a contingency analysis, we evaluated the accuracy of [¹⁸F]FDG-PET scan interpretation and plasma p-tau217 for an AD biomarker profile in CSF and for amyloid-PET positivity. A total of 81 individuals with early onset and/or atypical dementia were included in this study (mean age = 65 years; 48/81 female (59%). Both [¹⁸F]FDG-PET and plasma p-tau217 showed high levels of agreement with reference standard AD biomarkers ([¹⁸F]FDG-PET area under the curve [AUC]: 71%; plasma p-tau217 AUC: 81%). Although both biomarkers had similar specificity for AD [¹⁸F]FDG-PET: 70%, CI: 0.56-0.81; plasma p-tau217: 70%, CI: 0.56-0.81), plasma p-tau217 had higher sensitivity for AD (plasma p-tau217: 97%, CI: 0.85-0.99 vs [¹⁸F]FDG-PET: 73%, CI: 0.57-0.85) (<i>p</i> = 0.01). Overall accuracy was also higher for plasma p-tau217 (AUC = 84%, CI: 0.75-0.93 vs 72%, CI: 0.60-0.83 of [¹⁸F]FDG-PET) (<i>p</i> = 0.02). The same pattern of results was observed when using amyloid-PET as the reference standard. Our study provides evidence that plasma p-tau217 has strong discriminative accuracy for AD among patients with early-onset and/or atypical dementia assessed in specialized settings. Future work should replicate these findings in secondary care settings.