White Matter Hyperintensity as a Vascular Contribution to the AT(N) Framework.

Area of Science:

• Neurology
• Biomarkers
• Neurodegenerative Diseases

Background:

• The AT(N) framework stages Alzheimer's disease (AD) biologically via amyloid-beta (Aβ), tau (T), and neurodegeneration (N) biomarkers.
• Cerebrovascular disease (CVD), particularly white matter hyperintensities (WMH) from chronic ischemia, is implicated in AD etiology.
• The relationship between WMH and AD's core Aβ and tau pathologies is not fully understood.

Approach:

• This review synthesizes existing studies examining the association between WMH and AD pathophysiology (Aβ and tau).
• It highlights the need for further research into WMH's role in AD progression.

Key Points:

• Evidence linking WMH to Aβ pathology in AD is inconsistent, potentially due to WMH load and location.
• More research is necessary to clarify the association between WMH and tau pathology.
• Longitudinal studies with standardized WMH quantification are crucial.

Conclusions:

• WMH may serve as a vascular biomarker within the AT(N) framework for AD.
• Further investigation into novel CVD biomarkers could illuminate CVD's contribution to AD.
• Harmonized methodologies are needed to validate WMH's role in the AT(N) classification.