Where Do Plasma Biomarkers fit in With Current Alzheimer's Disease Detection?

Objectives: We examine the clinical utility of plasma-based detection for Alzheimer's disease (AD) pathophysiology in older adults with mild cognitive impairment (MCI) and whether cognitive screening can inform when to use adults with MCI had testing with plasma phosphorylated tau (p-tau) 217 and 181, positron emission tomography (PET) imaging for amyloid beta (Ab), and cognitive assessment. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of plasma p-tau. Results: Plasma p-tau217 distinguished MCI participants who had PET imaging evidence of Ab accumulation from those without (AUC of 0.92, specificity of 0.96, and sensitivity of 0.90), outperforming plasma p-tau181 (AUC of 0.76, specificity of 0.87 and sensitivity of 0.59) for the same purpose. Of the 60 MCI participants that were amnestic, 22 were Ab+. The 14 participants that were nonamnestic were all Ab-. Conclusions: Our findings support the clinical use of plasma p-tau, particularly p-tau217, for patient detection of AD pathophysiology in older adults with amnestic MCI, but not in those who are nonamnestic. (Am J Geriatr Psychiatry 2025; 33:428-437)