Peripheral TARC (CCL17) Levels Track Widespread Microstructural Vulnerability in Cognitively Unimpaired Older African...

Area of Science:

• Neuroscience
• Immunology
• Radiology

Background:

• Neuroinflammation and immune dysregulation are early drivers of Alzheimer's disease and AD-related dementias (AD/ADRD).
• Non-invasive biomarkers are needed to capture early AD/ADRD processes, especially in underrepresented African American populations.
• This study investigated systemic inflammation and brain microstructure in cognitively unimpaired older African Americans.

Purpose of the Study:

• To examine the relationship between plasma inflammatory markers and brain microstructural integrity.
• To identify potential non-invasive biomarkers for early AD/ADRD detection in African Americans.
• To assess the utility of diffusion MRI in detecting inflammation-related brain changes.

Main Methods:

• Forty-one cognitively unimpaired older African Americans underwent MRI and plasma inflammatory marker quantification.
• Diffusion Weighted Imaging (DWI) metrics (MD, RD, MK, RK) assessed brain microstructure.
• Voxel-wise and cluster-based general linear models analyzed associations between plasma markers and brain metrics.

Main Results:

• Higher TARC levels were linked to increased mean diffusivity (MD) and radial diffusivity (RD) in gray and white matter, indicating reduced microstructural integrity and potential myelin disruption.
• Kurtosis metrics (MK, RK) showed weaker, more selective associations, primarily decreases in white matter tracts.
• Cluster analyses confirmed diffusivity findings and consistent effect sizes across regions.

Conclusions:

• Elevated TARC is associated with early microstructural alterations detectable by diffusion MRI.
• Diffusivity metrics are more sensitive to inflammation-related changes than kurtosis measures in this cohort.
• Diffusion MRI and inflammatory biomarkers are promising for detecting early AD/ADRD neurobiological signatures in African Americans.