Alzheimer's disease biological PET staging using plasma p217+tau

Area of Science:

• Neurology
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Plasma phospho-tau biomarkers, like p217+tau, are effective in detecting Alzheimer's disease (AD) neuropathology.
• The utility of plasma biomarkers in replacing tau PET for determining AD biological staging remains under investigation.

Purpose of the Study:

• To evaluate the efficacy of plasma p217+tau in identifying and staging Alzheimer's disease (AD) biological progression.
• To compare the diagnostic performance of plasma p217+tau against established Aβ-PET and tau-PET imaging criteria.

Main Methods:

• Utilized plasma p217+tau, Aβ-PET, and tau-PET data from 248 cognitively unimpaired and 227 cognitively impaired individuals.
• Defined AD biological stages (Initial, Early, Intermediate, Advanced) based on Revised Criteria for Diagnosis and Staging of Alzheimer's Disease (2024).
• Assessed plasma p217+tau's performance in discriminating AD stages using ROC analysis and logistic regression.

Main Results:

• Plasma p217+tau concentrations correlated with AD biological PET stages.
• High diagnostic accuracy (AUC > 0.90) was observed for screening all AD stages and identifying combined Intermediate/Advanced stages.
• Plasma p217+tau demonstrated good sensitivity and specificity for Intermediate/Advanced AD stages, with high NPV for the Advanced stage.

Conclusions:

• Plasma p217+tau effectively screens for amyloid-positive (A+) individuals.
• Plasma p217+tau can identify individuals with combined Intermediate/Advanced AD stages.
• This biomarker may serve as a pre-screening tool to optimize the use of tau-PET imaging for identifying individuals with Advanced stage AD.