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Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease
Christopher Brown1, Sandhitsu Das1, Long Xie2,3
1Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Introduction:
Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages.
Methods:
Participants had dMRI and either beta-amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed post mortem 3D-map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages.
Results:
There was higher isometric volume fraction in amyloid-positive compared to amyloid-negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and 18F-flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages.
Discussion:
Combining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease. Highlights Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's. dMRI measured microstructure in regions with high NFT. Microstructural changes occur in medial temporal regions in preclinical disease. Microstructural changes occur in other typical Alzheimer's regions in later stages. Combining post mortem pathology atlases with in vivo MRI is a powerful framework.
Insights
Diffusion MRI detects early Alzheimer's neurodegeneration in preclinical stages. Microstructural changes in the medial temporal lobe indicate disease presence before significant cognitive decline.
Area of Science:
- Neuroimaging
- Neurodegeneration
- Alzheimer's Disease
Background:
- Standard MRI lacks sensitivity for early neurodegeneration.
- Diffusion MRI (dMRI) offers potential for detecting preclinical disease.
- Alzheimer's disease (AD) pathology can be detected years before symptoms manifest.
Purpose of the Study:
- To investigate if dMRI microstructural measures can detect neurodegeneration in preclinical Alzheimer's disease.
- To correlate dMRI findings with established Alzheimer's biomarkers.
- To map microstructural changes in relation to neurofibrillary tangle (NFT) burden.
Main Methods:
- Participants underwent dMRI and received beta-amyloid PET or plasma biomarker tests.
- Microstructure was analyzed in medial temporal lobe (MTL) regions with high, post-mortem-defined NFT burden.
- Regression analyses examined associations between microstructure and AD pathology markers across disease stages.
Main Results:
- Amyloid-positive individuals showed higher isometric volume fraction in high-NFT MTL regions.
- Plasma biomarkers and 18F-flortaucipir correlated with microstructural changes in preclinical AD.
- Further microstructural alterations were observed in typical AD regions during later disease stages.
Conclusions:
- Combining post-mortem NFT atlases with in vivo dMRI enables detection of preclinical AD neurodegeneration.
- dMRI microstructural analysis is sensitive to early pathological changes in AD.
- This integrated approach provides a powerful framework for understanding early AD progression.
