Alzheimer's Imaging Consortium

Area of Science:

• Neuroscience
• Biomarkers
• Neuroimaging

Background:

• Pro-inflammatory astrocyte activation, choroid plexus dysfunction, and ventricular enlargement impair cerebrospinal fluid (CSF) clearance.
• Dysregulated CSF clearance may contribute to Alzheimer's disease (AD) pathogenesis by facilitating amyloid-β and tau aggregation.
• This study investigated the role of ventricular remodeling and astrocyte activation in AD-related protein accumulation.

Purpose of the Study:

• To investigate the association between ventricular remodeling, astrocyte activation, and amyloid-β and tau accumulation in AD.
• To determine if astrocyte activation and ventricular remodeling drive protein aggregation and cognitive decline.
• To identify potential biomarkers for accelerated disease progression in AD.

Main Methods:

• Analysis of multimodal neuroimaging (MRI, PET) and fluid biomarker data from 500 participants in the TRIAD cohort.
• Utilized [18F]AZD4694 and [18F]MK6240 PET tracers for amyloid-β and tau, respectively.
• Assessed associations between ventricular/choroid plexus volumes, plasma GFAP (astrocyte marker), and amyloid-β/tau burden using region-of-interest and voxel-wise approaches.

Main Results:

• Reduced ventricular radioactivity and increased ventricular/choroid plexus volumes correlated with amyloid-β and tau pathology.
• Amyloid-β accumulation was significantly associated with ventricular volume and GFAP levels.
• Elevated GFAP, ventricular volume, and choroid plexus volume predicted faster cognitive decline, independent of amyloid-β and tau loads.

Conclusions:

• Astrocyte activation and ventricular remodeling independently contribute to early amyloid-β and tau aggregation in AD.
• Elevated GFAP and enlarged ventricles may serve as biomarkers for individuals at risk of accelerated AD progression.
• These findings underscore the critical role of CSF clearance in AD pathophysiology.