Basic Science and Pathogenesis

Area of Science:

• Neuroimaging
• Neurodegeneration
• Alzheimer's Disease

Background:

• Prior research indicates sulci are uniquely affected by aging and Alzheimer's disease (AD) pathology.
• The specific vulnerability of sulci to tau pathology and its cognitive impact remain unclear.
• Hypothesized unique connectivity patterns in sulcal depths warrant investigation regarding tau accumulation.

Purpose of the Study:

• To investigate whether tau-related atrophy preferentially affects sulci and their depths.
• To explore the relationship between tau pathology, cortical thinning, and cognitive function.
• To examine the role of hippocampal connectivity in tau-related vulnerability.

Main Methods:

• Utilized 3T MRI and amyloid/tau PET scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
• Correlated cortical thickness with neocortical tau levels using FreeSurfer's GLM pipeline.
• Analyzed overlap between tau-thickness correlation clusters and specific regions (gyri, sulci, sulcal depths); examined vertex-wise correlations and memory prediction; assessed postmortem tau and resting-state connectivity.

Main Results:

• Tau-thickness correlation clusters showed significantly greater overlap with sulci and sulcal depths compared to gyri.
• Sulcal regions exhibited higher tau-related cortical thinning (t-values) than gyral regions.
• The volume of tau-affected clusters strongly predicted memory performance; postmortem analysis confirmed higher tau in sulci, and resting-state connectivity was stronger in tau-affected regions.

Conclusions:

• Tau-related cortical thinning predominantly occurs in sulci, particularly in the depths.
• This sulcal vulnerability is potentially linked to increased tau accumulation in these regions.
• Enhanced hippocampal connectivity to vulnerable sulcal regions may contribute to tau pathology and cognitive decline.