Diffusion MRI detects early brain microstructure abnormalities in 2-month-old 3×Tg-AD mice

Area of Science:

• Neuroscience
• Biomedical Imaging
• Alzheimer's Disease Research

Background:

• The 3×Tg-AD mouse model mimics Alzheimer's disease (AD) pathology, including amyloid and tau hallmarks.
• Early white matter abnormalities, particularly in myelination, are observed in this model but are inconsistently studied with diffusion MRI (dMRI).

Purpose of the Study:

• To evaluate the sensitivity of dMRI in detecting early microstructural brain alterations in 2-month-old 3×Tg-AD mice.
• To investigate dMRI-detectable changes associated with myelination abnormalities preceding overt AD pathology.

Main Methods:

• Utilized diffusion MRI (dMRI) to assess brain microstructure in young (2-month-old) 3×Tg-AD mice and age-matched controls.
• Performed quantitative analysis of dMRI metrics (FA, KFA, K┴, MD, D┴) in specific brain regions (fimbria, fornix, hippocampus).
• Quantified myelin basic protein (MBP) immunoreactivity to assess myelination morphology.

Main Results:

• Significantly lower fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), and radial kurtosis (K┴) were observed in the fimbria of 3×Tg-AD mice.
• Elevated mean diffusivity (MD) and radial diffusivity (D┴) were found in the fimbria, dorsal hippocampus, and ventral hippocampus of 3×Tg-AD mice.
• Reduced myelin basic protein (MBP) immunoreactivity in the fimbria confirmed myelin abnormalities in 3×Tg-AD mice.

Conclusions:

• dMRI can detect widespread and significant early brain morphological abnormalities in young 3×Tg-AD mice.
• These dMRI findings are associated with myelin abnormalities, appearing before the onset of established Alzheimer's disease pathology.
• dMRI is a sensitive tool for identifying preclinical white matter changes in AD models.