The study evaluates the clinical value of the plasma ALZpath pTau217 immunoassay in assessing mild cognitive impairment (MCI). The BALTAZAR cohort, consisting of 473 participants with MCI, was analyzed to determine the performance of pTau181 and pTau217 in predicting amyloid status, cognitive decline, and conversion to Alzheimer's dementia. Results showed that pTau217 levels were significantly higher in Aβ+ individuals compared to Aβ- individuals, with a higher fold change than pTau181. The area under the curve (AUC) for predicting Aβ+ was 0.914 for pTau217, compared to 0.783 for pTau181. pTau217 also showed better predictive power for cognitive decline and conversion to dementia, with a higher hazard ratio (HR) than pTau181. The study found that pTau217 levels were not significantly affected by age, APOEε4 status, or renal dysfunction, suggesting its robustness in clinical settings. The optimal cut-points for pTau217 were determined as 0.44 pg/mL for detecting Aβ+ and 0.8 pg/mL for a 95% positive predictive value. These thresholds were associated with high conversion rates to dementia and significant cognitive decline. The study concludes that plasma pTau217 is a valuable biomarker for diagnosing cerebral amyloidosis and predicting cognitive decline and conversion to Alzheimer's dementia. The ALZpath pTau217 assay is a commercially available, scalable test that shows promising performance in clinical settings. The study highlights the importance of using pTau217 in clinical practice for early detection and management of Alzheimer's disease.The study evaluates the clinical value of the plasma ALZpath pTau217 immunoassay in assessing mild cognitive impairment (MCI). The BALTAZAR cohort, consisting of 473 participants with MCI, was analyzed to determine the performance of pTau181 and pTau217 in predicting amyloid status, cognitive decline, and conversion to Alzheimer's dementia. Results showed that pTau217 levels were significantly higher in Aβ+ individuals compared to Aβ- individuals, with a higher fold change than pTau181. The area under the curve (AUC) for predicting Aβ+ was 0.914 for pTau217, compared to 0.783 for pTau181. pTau217 also showed better predictive power for cognitive decline and conversion to dementia, with a higher hazard ratio (HR) than pTau181. The study found that pTau217 levels were not significantly affected by age, APOEε4 status, or renal dysfunction, suggesting its robustness in clinical settings. The optimal cut-points for pTau217 were determined as 0.44 pg/mL for detecting Aβ+ and 0.8 pg/mL for a 95% positive predictive value. These thresholds were associated with high conversion rates to dementia and significant cognitive decline. The study concludes that plasma pTau217 is a valuable biomarker for diagnosing cerebral amyloidosis and predicting cognitive decline and conversion to Alzheimer's dementia. The ALZpath pTau217 assay is a commercially available, scalable test that shows promising performance in clinical settings. The study highlights the importance of using pTau217 in clinical practice for early detection and management of Alzheimer's disease.