Neuropathological links between plasma p-Tau 181, white matter hyperintensity, and structural brain changes in aging.

Area of Science:

• Neuroimaging
• Neuropathology
• Gerontology

Background:

• White matter hyperintensity (WMH) is associated with brain structure changes and Alzheimer's disease (AD) pathology during aging.
• Understanding the mechanisms linking cerebrovascular pathology, structural brain changes, and AD pathology is crucial for aging research.

Purpose of the Study:

• To explore the underlying mechanisms linking cerebrovascular pathology, structural brain changes, and AD pathology in the aging process.
• To investigate the association between white matter hyperintensity (WMH) burden, plasma biomarkers of AD, and brain structure changes in cognitively normal elderly individuals.

Main Methods:

• Retrospective analysis of MRI scans and plasma samples from 218 cognitively normal elderly individuals.
• Stratification into mild (n=113) and severe (n=105) WMH groups using Fazekas scores.
• Assessment of cortical thickness, subcortical nucleus volumes, plasma amyloid-beta (Aβ)42 and phosphorylated tau (p-Tau) 181 levels, and cerebral small vessel disease (CSVD) markers. Mediation analysis was used to evaluate the role of WMH burden.

Main Results:

• Severe WMH group showed older age and higher plasma p-Tau 181 levels compared to the mild WMH group.
• Severe WMH was associated with left caudate nucleus enlargement.
• Plasma p-Tau 181 levels positively correlated with WMH severity (Fazekas scores).
• WMH burden partially mediated the relationship between plasma p-Tau 181 levels and left caudate nucleus enlargement.

Conclusions:

• Severe WMH is linked to caudate nucleus enlargement in aging individuals.
• WMH may act as a mediator between elevated plasma p-Tau 181 and caudate nucleus enlargement, suggesting mixed pathologies.
• Emphasizes the importance of controlling vascular risk factors for brain health during aging.