Prognostic value of plasma brain-derived pTau

Area of Science:

• Neurodegenerative diseases
• Biomarker discovery
• Alzheimer's disease research

Background:

• Plasma biomarkers are crucial for Alzheimer's disease (AD) diagnosis and prognosis.
• Brain-derived pTau217 (BD-pTau217) may offer greater AD specificity than total pTau217.
• The prognostic value of BD-pTau217 for predicting clinical and amyloid progression remains unclear.

Purpose of the Study:

• To compare the prognostic value of BD-pTau217 versus total plasma pTau217.
• To assess their ability to predict clinical and amyloid PET progression in cognitively unimpaired (CU) individuals.
• To evaluate biomarker performance in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

Main Methods:

• Utilized plasma biomarker data from 1,427 ADNI participants, including 529 CU individuals.
• Assessed amyloid PET progression in baseline CU amyloid-negative participants using longitudinal PET imaging.
• Employed Cox models and time-dependent AUC to evaluate associations between biomarkers and progression.

Main Results:

• BD-pTau217 did not significantly outperform total pTau217 in predicting progression to mild cognitive impairment or dementia.
• However, BD-pTau217 demonstrated superior prediction of amyloid PET positivity at 2.5 and 4 years in amyloid-negative participants (tdAUC 0.82 vs 0.69 and 0.77 vs 0.64, respectively).
• Hazard ratios indicated a significantly higher risk of progression with elevated BD-pTau217.

Conclusions:

• BD-pTau217 enhances the prediction of near-term amyloid PET progression in cognitively unimpaired individuals.
• The advantage of BD-pTau217 for predicting clinical progression is less pronounced.
• Plasma BD-pTau217 shows potential as a sensitive biomarker for early AD-related changes.