Evidence for Tau and Amyloid Pathology to Drive White Matter Damage in the Brain
Researchers here present indirect evidence for the toxic aggregation of amyloid-β and tau protein in the aging brain to drive the accumulation of white matter hyperintensities seen in brain imaging. These hyperintensities are areas of damage, resulting from a range of causes that include rupture of blood vessels, localized inflammatory response, and more. The more white matter damage in the brain, the worse the outcome in terms of cognitive loss and progression of neurodegenerative conditions.
White matter hyperintensities (WMHs) are increasingly recognized as markers of cerebrovascular pathology in Alzheimer's disease (AD), yet their temporal relationship with amyloid and tau accumulation remains unclear. While previous studies suggest bidirectional associations between WMHs and AD pathology, regional associations between WMHs and AD pathology have yet to be examined. This study investigated the temporal and regional associations between PET measures of amyloid (Aβ) and tau pathology and WMH burden in older adults.
Baseline analyses revealed significant bidirectional associations between WMH burden and both Aβ and tau pathology, with stronger effects in posterior brain regions. Longitudinal analyses showed that baseline Aβ levels were associated with future WMH progression in frontal and occipital regions, while baseline tau was linked to WMH increases in frontal and parietal regions. However, baseline WMH burden was not associated with future accumulation of either Aβ or tau pathology in any region. These findings suggest that Aβ and tau pathology drive future WMH progression rather than the reverse, with distinct regional patterns for each pathology type.