Three-Dimensional β-Amyloid Burden Correlation Between the Eye and Brain in Alzheimer's Disease Mice Using...

Area of Science:

• Neuroscience
• Ophthalmology
• Biomedical Imaging

Background:

• Peripheral beta-amyloid (Aβ) deposition is increasingly recognized for its role in Alzheimer's disease (AD).
• The eye is a potential site for early AD detection, but previous 2D studies lacked correlation with 3D brain pathology.
• Establishing a link between ocular and cerebral Aβ requires advanced imaging techniques that preserve tissue integrity.

Purpose of the Study:

• To assess the correlation between three-dimensional (3D) Aβ burden in the eyeball and brain using a combined PET/MR and LSFM platform.
• To investigate the potential of ocular Aβ as an early indicator of AD pathology.
• To explore the systemic nature of Aβ accumulation in AD.

Main Methods:

• Utilized a combined brain amyloid positron emission tomography/magnetic resonance (PET/MR) and light-sheet fluorescence microscopy (LSFM) platform.
• Collected and processed 13 mouse eyeballs and 17 mouse brains from 5xFAD AD models and controls.
• Quantified 3D Aβ plaque-like surface volumes and analyzed microglial and astrocyte markers.

Main Results:

• Significantly greater 3D plaque-like surface volumes were observed in AD eyeballs compared to controls (P = 0.001).
• AD brains showed higher [18F]Flutemetamol uptake and significantly greater 3D plaque-like surface volumes than controls (P < 0.001).
• A strong positive correlation (r = 0.810, P = 0.001) was found between 3D Aβ burden in the brain and eyeball.

Conclusions:

• The study demonstrates a strong correlation between 3D Aβ burden in the eyeball and brain.
• Ocular Aβ accumulation is a significant indicator of cerebral Aβ pathology.
• Peripheral Aβ in the eye may serve as an independent predictor of brain Aβ burden in Alzheimer's disease.