This study evaluates the diagnostic performance of plasma pTau217, pTau181, Aβ1-42, and Aβ1-40 measured using the LUMIPULSE automated platform for detecting Alzheimer's disease (AD). The study included 290 participants (66 cognitively unimpaired, 130 with mild cognitive impairment, and 94 with dementia) who underwent lumbar puncture in a specialized memory clinic. Participants were classified as amyloid positive (A+) or negative (A-) based on CSF Aβ1-42/Aβ1-40 ratios. Plasma concentrations of pTau217 and pTau181 were higher in A+ than in A- groups, while the Aβ1-42/Aβ1-40 ratio was lower in A+ groups. pTau181 and the Aβ1-42/Aβ1-40 ratio showed moderate correlations between plasma and CSF. The areas under the ROC curve for discriminating A+ from A- participants were 0.94 for pTau217 and 0.88 for pTau181 and Aβ1-42/Aβ1-40. pTau217 had the highest fold change (4.42) and showed high predictive capability with a misclassification rate of 4-7%. The global accuracy of pTau217 using a two-threshold approach was robust across symptomatic groups, exceeding 90%. The study concludes that the automated platform exhibits high diagnostic accuracy for AD pathophysiology, with pTau217 showing excellent diagnostic accuracy for identifying AD in a consecutive sample from a specialized memory clinic.This study evaluates the diagnostic performance of plasma pTau217, pTau181, Aβ1-42, and Aβ1-40 measured using the LUMIPULSE automated platform for detecting Alzheimer's disease (AD). The study included 290 participants (66 cognitively unimpaired, 130 with mild cognitive impairment, and 94 with dementia) who underwent lumbar puncture in a specialized memory clinic. Participants were classified as amyloid positive (A+) or negative (A-) based on CSF Aβ1-42/Aβ1-40 ratios. Plasma concentrations of pTau217 and pTau181 were higher in A+ than in A- groups, while the Aβ1-42/Aβ1-40 ratio was lower in A+ groups. pTau181 and the Aβ1-42/Aβ1-40 ratio showed moderate correlations between plasma and CSF. The areas under the ROC curve for discriminating A+ from A- participants were 0.94 for pTau217 and 0.88 for pTau181 and Aβ1-42/Aβ1-40. pTau217 had the highest fold change (4.42) and showed high predictive capability with a misclassification rate of 4-7%. The global accuracy of pTau217 using a two-threshold approach was robust across symptomatic groups, exceeding 90%. The study concludes that the automated platform exhibits high diagnostic accuracy for AD pathophysiology, with pTau217 showing excellent diagnostic accuracy for identifying AD in a consecutive sample from a specialized memory clinic.