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The clinical diagnosis groups had annual cognitive (Mini\u2010Mental State Examination, MMSE) and functional (Clinical Dementia Rating Scale, CDR) measures. NC (<jats:italic>N<\/jats:italic>\u00a0=\u00a070), MCI (<jats:italic>N<\/jats:italic>\u00a0=\u00a075), and AD dementia (<jats:italic>N<\/jats:italic>\u00a0=\u00a050) cases from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used as a validation cohort. Plasma p\u2010tau181 was measured using the Quanterix SiMoA HD\u2010X platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma p\u2010tau181 differentiated pathology\u2010confirmed AD from NC with negative amyloid PET scans with an AUC of 0.93. A cut point of 3.44\u2009pg\/mL (maximum Youden Index) had a sensitivity of 0.77, specificity of 0.96. p\u2010Tau181 values above the cut point were associated with the faster rate of decline in MMSE in AD dementia and MCI and a shorter time to a clinically significant functional decline in all groups. In a subset of MCI cases from ADNI, p\u2010tau181 values above the cut point associated with faster rate of decline in MMSE, and a shorter time to a clinically significant functional decline and conversion to dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Plasma p\u2010tau181 differentiates AD pathology cases from NC with high accuracy. 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