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Updated: Jul 1, 2025
Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Diffusion MRI relates to plasma Aβ42/40 in PET negative participants without dementia
Jesse C DeSimone1,2, Wei-En Wang1,2, David A Loewenstein2,3,4
1Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, Florida, USA.
Introduction:
Magnetic resonance imaging (MRI) biomarkers are needed for indexing early biological stages of Alzheimer's disease (AD), such as plasma amyloid-β (Aβ42/40) positivity in Aβ positron emission tomography (PET) negative individuals.
Methods:
Diffusion free-water (FW) MRI was acquired in individuals with normal cognition (NC) and mild cognitive impairment (MCI) with Aβ plasma-/PET- (NC = 22, MCI = 60), plasma+/PET- (NC = 5, MCI = 20), and plasma+/PET+ (AD dementia = 21) biomarker status. Gray and white matter FW and fractional anisotropy (FAt) were compared cross-sectionally and the relationships between imaging, plasma and PET biomarkers were assessed.
Results:
Plasma+/PET- demonstrated increased FW (24 regions) and decreased FAt (66 regions) compared to plasma-/PET-. FW (16 regions) and FAt (51 regions) were increased in plasma+/PET+ compared to plasma+/PET-. Composite brain FW correlated with plasma Aβ42/40 and p-tau181.
Discussion:
FW imaging changes distinguish plasma Aβ42/40 positive and negative groups, independent of group differences in cognitive status, Aβ PET status, and other plasma biomarkers (i.e., t-tau, p-tau181, glial fibrillary acidic protein, neurofilament light).
Highlights:
Plasma Aβ42/40 positivity is associated with brain microstructure decline. Plasma+/PET- demonstrated increased FW in 24 total GM and WM regions. Plasma+/PET- demonstrated decreased FAt in 66 total GM and WM regions. Whole-brain FW correlated with plasma Aβ42/40 and p-tau181 measures. Plasma+/PET- demonstrated decreased cortical volume and thickness.
Insights
Plasma amyloid-β positivity indicates brain microstructure decline, detectable with free-water diffusion MRI. This imaging biomarker is sensitive to early Alzheimer's disease changes, even before PET scans show amyloid accumulation.
Area of Science:
- Neuroimaging
- Biomarkers
- Alzheimer's Disease Research
Background:
- Early detection of Alzheimer's disease (AD) requires sensitive biomarkers for preclinical stages.
- Plasma amyloid-β (Aβ) positivity, particularly Aβ42/40 ratio, shows promise but needs correlation with in-vivo brain changes.
- Magnetic Resonance Imaging (MRI) offers potential for assessing brain microstructure alterations associated with AD pathology.
Purpose of the Study:
- To investigate the utility of diffusion free-water (FW) MRI as a biomarker for early Alzheimer's disease.
- To correlate FW and fractional anisotropy (FAt) changes with plasma Aβ status in individuals with normal cognition and mild cognitive impairment.
- To assess if FW MRI can distinguish between different stages of AD biomarker positivity.
Main Methods:
- Diffusion free-water (FW) MRI and fractional anisotropy (FAt) were acquired in individuals categorized by plasma and Aβ positron emission tomography (PET) status.
- Groups included normal cognition (NC) and mild cognitive impairment (MCI) with plasma-/PET-, plasma+/PET-, and plasma+/PET+ (AD dementia) biomarker profiles.
- Cross-sectional comparisons of gray and white matter FW and FAt were performed, alongside correlation analyses with plasma and PET biomarkers.
Main Results:
- Individuals with plasma Aβ positivity (plasma+/PET-) showed increased FW in 24 regions and decreased FAt in 66 regions compared to plasma-/PET-.
- Plasma+/PET+ individuals exhibited increased FW (16 regions) and decreased FAt (51 regions) compared to plasma+/PET-.
- Composite brain FW demonstrated correlations with plasma Aβ42/40 and p-tau181 levels.
Conclusions:
- Free-water diffusion MRI changes are indicative of brain microstructure decline associated with plasma Aβ42/40 positivity.
- FW imaging can differentiate between plasma Aβ positive and negative groups, independent of cognitive status and other biomarkers.
- Plasma Aβ positivity is linked to early neurodegenerative changes detectable by advanced MRI techniques.
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