Biomarkers

Area of Science:

• Neuroimaging
• Alzheimer's Disease Research
• Biomarker Discovery

Background:

• Spatiotemporal tau accumulation patterns vary across Alzheimer's disease (AD) phenotypes.
• Tau PET imaging can identify these patterns, potentially influenced by amyloid-beta (Aβ) deposition and network connectivity (RSFC).

Purpose of the Study:

• To replicate tau PET subtypes using the SuStaIn model.
• To investigate subtype-specific differences in Aβ PET deposition and RSFC patterns.

Main Methods:

• Utilized the Subtype and Stage Inference (SuStaIn) model on 820 tau PET scans from 629 participants.
• Analyzed resting-state functional connectivity (RSFC) and amyloid-beta (Aβ) PET (PiB or FBP) data.
• Harmonized Aβ PET data to Centiloid for standardized comparison.

Main Results:

• Identified three tau PET subtypes: limbic predominant, posterior predominant, and MTL-sparing.
• MTL-sparing subtype showed younger age, greater impairment, and higher Aβ PET levels.
• Posterior predominant subtype exhibited distinct RSFC patterns and lower Aβ PET in some regions compared to limbic predominant.

Conclusions:

• Replicated three distinct tau PET subtypes in an independent AD cohort.
• Observed novel differences in Aβ PET and RSFC spatial patterns specific to each subtype.
• These subtype-specific network and deposition patterns may influence tau spreading in AD.