Biomarkers

Area of Science:

• Neuroimaging
• Neuropathology
• Alzheimer's Disease Research

Background:

• The Harvard Aging Brain Study (HABS) investigates differences between normal aging and preclinical Alzheimer's Disease (AD).
• Sixteen HABS participants donated their brains for neuropathologic assessment.
• This study evaluates the predictive power of antemortem PET biomarkers for neuropathologic findings.

Purpose of the Study:

• To compare antemortem PET biomarkers with postmortem neuropathologic assessments of amyloid-β and tau.
• To determine the extent to which PET imaging can predict the spatial distribution and density of neuropathologic changes.
• To identify potential discrepancies between PET imaging and neuropathology, particularly for tau PET.

Main Methods:

• Neuropathologic assessments included amyloid-β plaques (Thal phase/A score), tau tangles (Braak NFT stage/B score), and neuritic plaques (CERAD NP score/C score).
• Amyloid-β PET (PiB) metrics included frontal, lateral temporal, parietal, and retrosplenial cortex distribution volume ratio (DVR) and spatial extent (EXT).
• Tau PET (flortaucipir, FTP) metrics included standardized uptake value ratios (SUVRs) in the whole temporal lobe, medial temporal lobe (MTL), and temporal neocortex (NEO-T), analyzed bilaterally and laterally.

Main Results:

• Amyloid-β PET (PiB) metrics (DVR and EXT) significantly correlated with amyloid-β plaque scores (A and C).
• Initial tau PET (FTP) SUVRs did not significantly correlate with Braak NFT stage (B score).
• After excluding outliers, whole temporal and NEO-T SUVRs correlated significantly with B score; lateralized SUVRs further strengthened these correlations.

Conclusions:

• Amyloid-β PET metrics accurately reflect amyloid plaque distribution and density.
• Tau PET metrics correlate with tau tangle distribution, but require outlier removal, suggesting potential discrepancies.
• Individualized tau PET metrics accounting for heterogeneity are proposed to enhance prediction of neuropathologic assessments.