Basic Science and Pathogenesis

Area of Science:

• Neuroimaging
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Microstructural brain changes precede Alzheimer's disease (AD) onset and cognitive decline.
• Early detection of these changes is crucial for understanding AD progression.
• The T1-weighted/T2-weighted (T1w/T2w) MRI ratio shows potential as a biomarker but requires further validation.

Purpose of the Study:

• To investigate the relationship between the T1w/T2w ratio and histological measures of microstructural changes in AD.
• To clarify the potential of the T1w/T2w ratio as a neuroimaging biomarker for AD and its subtypes.

Main Methods:

• Acquired postmortem in-situ and antemortem T1w/T2w MRI scans from AD and control brain donors.
• Processed MRI data to calculate standardized T1w/T2w ratios using SPM12 and the Brainnetome atlas.
• Performed immunostaining on brain tissue for myelin, neuro-axonal damage, microglia, iron, Aβ, and pTau, quantifying immunoreactivity.

Main Results:

• Postmortem AD brains exhibited a global decrease in T1w/T2w ratio compared to controls, most pronounced in the hippocampus and parahippocampus.
• The T1w/T2w ratio was lower in typical AD compared to atypical AD in (para)hippocampal regions.
• T1w/T2w ratios showed strong correlation between postmortem and antemortem scans and were associated with myelin, microglia, Aβ, pTau, neuro-axonal damage, and iron density in AD brains.

Conclusions:

• The T1w/T2w ratio serves as a broad indicator of cortical tissue integrity in AD, not limited to myelin.
• The T1w/T2w ratio can distinguish AD brains from controls and differentiate between AD subtypes.
• This study enhances the understanding and potential application of the T1w/T2w ratio in AD research and clinical settings.