Alzheimer's Imaging Consortium

Area of Science:

• Neuroscience
• Biomarkers
• Neuroimaging

Background:

• Alzheimer's disease (AD) diagnosis relies on expensive amyloid (Aβ) and tau-PET imaging, limiting their use for screening unimpaired populations.
• Research focuses on affordable methods for detecting pre-symptomatic AD pathology, including cognitive metrics and blood-based biomarkers like soluble phosphorylated tau (p-tau).
• Head-to-head comparisons of these emerging markers and their additive value for early AD detection are scarce.

Purpose of the Study:

• To investigate the utility of plasma p-tau217 and cognitive tasks in identifying clinically unimpaired (CU) individuals with PET-imaging evidence of AD pathology.
• To compare the diagnostic accuracy of plasma p-tau217 and specific cognitive tests for detecting early AD.
• To assess the additive value of combining plasma biomarkers and cognitive measures for early AD detection.

Main Methods:

• Eighty CU older adults underwent plasma p-tau217 testing, Aβ-PET and tau-PET scans, and neuropsychological assessments including the Conceptual Matching Task (CMT) and Visual-Short Term Memory Binding Test (VSTMBT).
• Participants were classified based on amyloid-PET (Aβ- or Aβ+) or tau-PET (Tau-CU or Tau+CU) status.
• Receiver operating characteristic (ROC) curves were used to determine the accuracy of individual and combined markers in differentiating PET-positive from PET-negative individuals.

Main Results:

• Plasma p-tau217 demonstrated the highest accuracy (AUC=0.91) in detecting incipient amyloidosis or tauopathy.
• The VSTMBT was the most sensitive cognitive measure for detecting Aβ (AUC=0.722) and tau-PET positivity (AUC=0.743).
• Combining plasma p-tau217 and cognitive markers achieved high accuracy (AUC=0.93 for Aβ, AUC=0.95 for tau) and improved sensitivity for detecting tau-PET positivity to 1.0.

Conclusions:

• The combination of plasma biomarkers and cognitive measures shows significant promise for the early diagnosis of Alzheimer's disease.
• This combined approach enhances the ability to identify preclinical AD pathology in clinically unimpaired individuals.
• Further research validating these combined markers could lead to more accessible AD screening tools.