Alzheimer's Imaging Consortium

Area of Science:

• Neuroimaging
• Alzheimer's Disease Research
• Biomarker Discovery

Background:

• Distinct Alzheimer's disease (AD) phenotypes exhibit varying tau accumulation patterns detectable by PET imaging.
• Tau spread may be influenced by neuronal network connectivity (estimated via resting-state functional connectivity MRI - RSFC) and amyloid-beta (Aβ) deposition.

Purpose of the Study:

• To replicate previously identified tau PET subtypes in a new cohort.
• To investigate subtype-specific differences in RSFC and Aβ PET patterns.

Main Methods:

• Utilized the Subtype and Stage Inference (SuStaIn) model on 820 tau PET scans (¹⁸F-flortaucipir).
• Analyzed RSFC correlations using seeds in the primary visual cortex (V1) and precuneus/posterior cingulate cortex (PCC).
• Harmonized Aβ PET SUVRs (¹¹C-Pittsburgh-compound-B or ¹⁸F-florbetapir) to Centiloid.

Main Results:

• Identified three tau PET subtypes: limbic predominant (N=157), posterior predominant (N=27), and medial temporal lobe (MTL)-sparing (N=52).
• MTL-sparing subtype showed younger age, greater impairment, and higher Aβ PET levels.
• Posterior predominant subtype displayed distinct RSFC patterns and lower Aβ PET in anterior regions compared to limbic predominant.

Conclusions:

• Successfully replicated three distinct spatiotemporal tau PET subtypes in an independent AD cohort.
• Observed novel subtype-specific differences in Aβ PET spatial patterns and RSFC.
• These findings suggest unique tau spreading mechanisms within different AD subtypes.