Plasma p-tau217 fails to reliably detect donanemab-induced amyloid clearance in early Alzheimer's disease.

Alzheimer's disease (AD) is characterized by amyloid-beta plaques and tau neurofibrillary tangles, leading to progressive neurodegeneration. Disease-modifying therapies like donanemab target amyloid plaques, necessitating reliable methods to monitor treatment-related amyloid clearance (TRAC). While plasma p-tau217 is a promising biomarker for early AD diagnosis and tau pathophysiology, its utility for non-invasively tracking amyloid plaque removal post-treatment has been unclear. Current monitoring relies on expensive and less accessible amyloid positron emission tomography (PET) scans.

Researchers analyzed data from the phase 3 TRAILBLAZER-ALZ 2 trial, enrolling 830 participants with early symptomatic Alzheimer's disease. Participants received donanemab treatment, and both amyloid PET scans and plasma p-tau217 levels were assessed at baseline and longitudinally. The study evaluated the diagnostic performance of plasma p-tau217 in detecting post-treatment TRAC, defined as an amyloid PET level below 24.1 Centiloids (CL). Receiver operating characteristic (ROC) analysis was used to determine the biomarker's accuracy.

Plasma p-tau217 demonstrated suboptimal performance in detecting treatment-related amyloid clearance (TRAC) as measured by PET in donanemab-treated participants.

Specifically, at 52 weeks, the area under the ROC curve (AUC) for plasma p-tau217 in detecting TRAC was 0.61. This value indicates a limited ability to differentiate between participants who achieved amyloid clearance and those who did not, falling short of what would be considered a reliable diagnostic or monitoring tool. Despite prior evidence showing reductions in plasma p-tau217 levels with donanemab treatment, this analysis confirms that these reductions do not translate into accurate detection of TRAC below the 24.1 CL threshold.