Alzheimer's Imaging Consortium.

Area of Science:

• Neuroscience
• Neuroimaging
• Alzheimer's Disease Research

Background:

• Pathological tau protein aggregates spread through the brain in an activity-dependent manner.
• Previous research indicates tau spread can be detected in vivo in regions connected to the entorhinal cortex (ERC).
• This study investigated if functional connectivity (FC) of the basal forebrain (BF), an early site of tau accumulation, also predicts tau spread patterns.

Purpose of the Study:

• To determine if functional connectivity (FC) of the basal forebrain (BF) predicts tau deposition patterns.
• To compare the predictive power of ERC and BF functional connectivity on tau spread.
• To explore the relationship between FC strength and tau accumulation in the cortex.

Main Methods:

• Tau-PET scans (flortaucipir) from unimpaired older adults (ADNI and BACS) were analyzed.
• Resting-state fMRI was used to generate seed-to-voxel FC networks for ERC and BF.
• Tau-PET uptake was compared within and outside FC networks using SUVR and voxel proportion methods.

Main Results:

• FC networks of both ERC and BF showed significantly higher tau-PET uptake compared to outside-network regions.
• The ERC seed demonstrated a stronger association between FC and tau deposition than the BF seed.
• Cortical tau accumulation strength was significantly correlated with the strength of functional connectivity to the ERC or BF.

Conclusions:

• Functional connectivity patterns in early tau accumulating regions like the ERC and BF predict tau deposition across the cortex.
• The ERC exhibits a more robust FC-mediated tau spread compared to the BF.
• Future studies will examine the influence of amyloid and APOE4 on FC-tau spread relationships.