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Tau PET and Plasma p ‐tau217 as Independent and Synergistic Predictors of Clinical Progression in Early Symptomatic AD Patients With Amyloid and Tau Pathology

Year: 2025

Type: article

Abstract: Background Blood‐based biomarkers have significant potential to aid in the diagnosis of Alzheimer's disease (AD), providing a more accessible option than cerebrospinal fluid testing or positron emission tomography (PET). The objective of this study is to evaluate the prognostic value of a plasma p ‐tau217 immunoassay and tau PET imaging with respect to clinical progression. Method Placebo‐treated, early symptomatic AD patients (all amyloid‐positive by amyloid PET) in the TRAILBLAZER‐ALZ 2 study (NCT04437511) were analyzed. Patients (starting cohort N = 857) were split into below and above median groups based on median values of baseline flortaucipir tau PET signal evaluated by global AD‐signature region‐of‐interest standardized uptake value ratios (Tau PET lower , Tau PET higher ) and baseline plasma p ‐tau217 levels ( p ‐tau217 lower , p ‐tau217 higher ). The following clinical measures were assessed at Week 76: least squares mean change from baseline in Clinical Dementia Rating ‐ Sum of Boxes (CDR‐SB) and integrated AD Rating Scale (iADRS). Time‐to‐event for the minimal clinically important difference in CDR Global score (CDR‐GS MCID), defined as any increase in CDR‐GS for 2 consecutive visits, was estimated using Kaplan‐Meier analyses. Hazard ratios (HR), 95% confidence intervals (CI), and p ‐values were calculated using Cox proportional hazards model. These analyses are detailed in the figures. Result At Week 76, significant differences compared to baseline in both CDR‐SB and iADRS were observed between patients with baseline Tau PET higher |P‐tau217 lower or Tau PET higher |P‐tau217 higher and those with baseline Tau PET lower |P‐tau217 lower ( p <0.001); although not statistically significant, a higher rate of clinical progression was observed in Tau PET lower |P‐tau217 higher than Tau PET lower |P‐tau217 lower (Figure 1). An increased risk of progressing to CDR‐GS MCID was observed in patients with baseline Tau PET higher |P‐tau217 higher (HR [95% CI]=1.9 [1.2‐3.1]; p <0.05) compared with those with baseline Tau PET lower |P‐tau217 lower (Figure 2). Conclusion Patients with both higher baseline Tau PET and p ‐tau217 showed a statistically significant clinical worsening at Week 76 compared with those with both lower baseline Tau PET and p ‐tau217. Results suggest that, although baseline values of tau PET imaging and p ‐tau217 alone predicted clinical worsening at Week 76, using both tau PET and p ‐tau217 provided a better prognostic value than tau PET or p ‐tau217 alone in patients with early symptomatic AD.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70856_106363