Alzheimer's Imaging Consortium | JoVE Visualize

Area of Science:

Neurology
Biomarker Discovery
Neuroimaging

Background:

Accurate staging of Alzheimer's disease neuropathologic changes (ADNC) is crucial for clinical trials and patient management.
In vivo tau-PET imaging is a reliable proxy for high ADNC, while plasma biomarkers like p-tau217 offer a minimally invasive alternative.
Evaluating the diagnostic performance of plasma p-tau217 against established neuropathologic and imaging standards is essential.

Purpose of the Study:

To assess the accuracy of commercially available plasma p-tau217 in identifying intermediate and high ADNC.
To compare plasma p-tau217 performance with in vivo tau-PET imaging for ADNC detection.
To determine the utility of plasma p-tau217 for biological staging and early Alzheimer's disease detection.

Main Methods:

Analysis of autopsy-confirmed ADNC, plasma p-tau217, and Aβ42/Aβ40 levels in ADNI and A4 study participants.
Visual assessment of [18F]flortaucipir tau-PET scans by trained readers using FDA/EMA-approved methods.
Receiver operating characteristic (ROC) curve analysis to evaluate the discriminative accuracy of plasma p-tau217 across different ADNC severity levels.

Main Results:

Plasma p-tau217 demonstrated high accuracy (AUC>0.93) in distinguishing between "no/low/intermediate" and "high" ADNC at autopsy.
While effective in identifying "no" or "high" ADNC (80-93%), plasma p-tau217 showed high variability in classifying low/intermediate ADNC (40-65% and 35-57% accuracy, respectively).
Findings were consistent with in vivo tau-PET data, where plasma biomarkers reliably identified high ADNC but struggled with intermediate or preclinical cases (A+T-).

Conclusions:

Plasma p-tau217 effectively identifies extreme ADNC stages but has limited reliability for intermediate levels, impacting its utility in biological disease staging.
The suboptimal performance in preclinical cases, including failure to reliably identify A+T- individuals, questions its role in early AD detection.
Complementary diagnostic tools, potentially including advanced imaging techniques, may be necessary to enhance the reliability of early-stage Alzheimer's disease assessment.