This study evaluates the clinical performance of plasma pTau181 and pTau217 as biomarkers for Alzheimer's disease (AD) in the BALTAZAR cohort, a well-characterized prospective multicentre cohort of participants with mild cognitive impairment (MCI). The primary findings indicate that plasma pTau217 is highly effective in detecting cerebral amyloidosis and predicting cognitive decline and conversion to AD dementia. - **Clinical Performance**: Plasma pTau217 levels were significantly higher in participants with MCI who were amyloid-positive (Aβ+) compared to those who were Aβ-. The area under the curve (AUC) for detecting Aβ+ was 0.914 for pTau217,优于 pTau181 的 0.783。 - **Cognitive Decline and Conversion**: High plasma pTau217 levels were associated with a higher risk of converting from MCI to AD dementia within 3 years, with a hazard ratio (HR) of 8.30 for pTau217 compared to 1.38 for pTau181. The optimal cut-point for detecting Aβ+ was 0.44 pg/mL, and for ruling out Aβ+, it was <0.23 pg/mL. - **Confounding Factors**: Renal function and other comorbidities had minimal impact on the performance of pTau217, unlike pTau181, which was significantly affected by impaired renal function. - **Clinical Implications**: The study suggests that plasma pTau217 can provide significant information for patient management, including diagnostic strategy, prevention, and access to disease-modifying therapies. The findings support the clinical use of pTau217 as a valuable tool in the management of AD.This study evaluates the clinical performance of plasma pTau181 and pTau217 as biomarkers for Alzheimer's disease (AD) in the BALTAZAR cohort, a well-characterized prospective multicentre cohort of participants with mild cognitive impairment (MCI). The primary findings indicate that plasma pTau217 is highly effective in detecting cerebral amyloidosis and predicting cognitive decline and conversion to AD dementia. - **Clinical Performance**: Plasma pTau217 levels were significantly higher in participants with MCI who were amyloid-positive (Aβ+) compared to those who were Aβ-. The area under the curve (AUC) for detecting Aβ+ was 0.914 for pTau217,优于 pTau181 的 0.783。 - **Cognitive Decline and Conversion**: High plasma pTau217 levels were associated with a higher risk of converting from MCI to AD dementia within 3 years, with a hazard ratio (HR) of 8.30 for pTau217 compared to 1.38 for pTau181. The optimal cut-point for detecting Aβ+ was 0.44 pg/mL, and for ruling out Aβ+, it was <0.23 pg/mL. - **Confounding Factors**: Renal function and other comorbidities had minimal impact on the performance of pTau217, unlike pTau181, which was significantly affected by impaired renal function. - **Clinical Implications**: The study suggests that plasma pTau217 can provide significant information for patient management, including diagnostic strategy, prevention, and access to disease-modifying therapies. The findings support the clinical use of pTau217 as a valuable tool in the management of AD.