White matter hyperintensities influence distal cortical β-amyloid accumulation in default mode network pathways
Doaa G Ali1,2, Ahmed A Bahrani1,3, Riham H El Khouli4
1Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
Background And Purpose:
Cerebral small vessel disease (SVD) has been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Yet, the role of SVD in potentially contributing to AD pathology is unclear. The main objective of this study was to test the hypothesis that WMHs influence amyloid β (Aβ) levels within connected default mode network (DMN) tracts and cortical regions in cognitively unimpaired older adults.
Methods:
Regional standard uptake value ratios (SUVr) from Aβ-PET and white matter hyperintensity (WMH) volumes from three-dimensional magnetic resonance imaging FLAIR images were analyzed across a sample of 72 clinically unimpaired (mini-mental state examination ≥26), older adults (mean age 74.96 and standard deviation 8.13) from the Alzheimer's Disease Neuroimaging Initiative (ADNI3). The association of WMH volumes in major fiber tracts projecting from cortical DMN regions and Aβ-PET SUVr in the connected cortical DMN regions was analyzed using linear regression models adjusted for age, sex, ApoE, and total brain volumes.
Results:
The regression analyses demonstrate that increased WMH volumes in the superior longitudinal fasciculus were associated with increased regional SUVr in the inferior parietal lobule (p = .011).
Conclusion:
The findings suggest that the relation between Aβ in parietal cortex is associated with SVD in downstream white matter (WM) pathways in preclinical AD. The biological relationships and interplay between Aβ and WM microstructure alterations that precede overt WMH development across the continuum of AD progression warrant further study.
Insights
Small vessel disease (SVD) impacts amyloid-beta (Aβ) levels in the brain
Area of Science:
- Neurology
- Neuroimaging
- Alzheimer's Disease Research
Background:
- Cerebral small vessel disease (SVD) is implicated in Alzheimer's disease (AD) pathogenesis.
- The precise role of SVD in AD pathology remains unclear.
- Investigating the link between white matter hyperintensities (WMH) and amyloid-beta (Aβ) in cognitively unimpaired older adults is crucial.
Purpose of the Study:
- To test if white matter hyperintensities (WMH) influence amyloid-beta (Aβ) levels.
- To examine Aβ levels within default mode network (DMN) tracts and cortical regions.
- To explore SVD's contribution to preclinical AD pathology.
Main Methods:
- Analyzed Aβ-PET SUVr and WMH volumes in 72 cognitively unimpaired older adults (ADNI3).
- Utilized 3D MRI FLAIR for WMH volume assessment.
- Employed linear regression adjusted for age, sex, ApoE, and total brain volume.
Main Results:
- Increased WMH in the superior longitudinal fasciculus correlated with higher Aβ-PET SUVr in the inferior parietal lobule (p=0.011).
- This suggests a link between SVD in white matter pathways and Aβ deposition in the parietal cortex.
Conclusions:
- Findings indicate an association between parietal Aβ and SVD in downstream white matter pathways in preclinical AD.
- Further research is needed on the interplay between Aβ and white matter alterations in AD progression.
- Understanding these relationships is key to unraveling AD pathogenesis.
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