Biomarkers.

Area of Science:

• Neurology
• Radiology
• Gerontology

Background:

• Preclinical Alzheimer's disease (AD) is characterized by amyloid buildup but preserved cognition.
• Most participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial lacked significant tau accumulation.
• The TRAILBLAZER-ALZ 3 trial investigates donanemab efficacy in preclinical AD.

Purpose of the Study:

• To characterize and compare baseline tau positron emission tomography (PET) scans from the TRAILBLAZER-ALZ 3, A4, and TRAILBLAZER-ALZ 2 studies.
• To analyze tau distribution in preclinical AD populations using flortaucipir F 18 (FTP) PET scans.

Main Methods:

• Utilized data from 310 participants in the TRAILBLAZER-ALZ 3 trial, categorized by Clinical Dementia Rating-Global Score (CDR-GS 0 and CDR-GS 0.5).
• Employed flortaucipir F 18 (FTP) tau PET imaging and an established pipeline for analyzing global tau burden and regional patterns.
• Defined tau positivity using standardized uptake value ratio (SUVR) cut points (>1.11 for positive scan, >1.46 for high tau level).

Main Results:

• 13.3% of CDR0 and 25.5% of CDR0.5 participants showed positive tau PET scans (SUVR > 1.11).
• Medial and lateral temporal lobes exhibited the highest regional baseline SUVRs in both subgroups.
• Average SUVRs indicated a sequential deposition pattern: medial temporal > lateral temporal > parietal > frontal lobes.

Conclusions:

• Baseline tau PET patterns in TRAILBLAZER-ALZ 3 are consistent with other preclinical AD populations, including the CDR0.5 subgroup.
• Observed tau deposition patterns support a sequential progression from medial temporal to frontal lobes.
• Further regional analyses are planned to provide deeper insights into tau distribution.