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 plasma-based AD tests. METHODS: Seventy-four community-dwelling older adults with MCI had testing with plasma phosphorylated tau (p-tau) 217 and 181, positron emission tomography (PET) imaging for amyloid beta (Aβ), 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 Aβ 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 Aβ+. The 14 participants that were nonamnestic were all Aβ-. 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.