White matter hyperintensities influence distal cortical β-amyloid accumulation in default mode network pathways

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.