Cortical tau load is associated with white matter hyperintensities

Area of Science:

• Neuroscience
• Neuropathology
• Radiology

Background:

• Cerebral white matter lesions (WMLs), or white matter hyperintensities (WMH), are linked to small vessel disease (SVD).
• Alternatively, WMH may result from axonal damage secondary to Alzheimer's disease (AD) pathologies like hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ).

Purpose of the Study:

• To investigate the independent contributions of HPτ, Aβ, and SVD to the severity of WMH.
• To determine if WMH in AD patients are primarily associated with AD pathology or SVD.

Main Methods:

• Post-mortem MRI of 36 human cerebral hemispheres assessed WMH using the Age Related White Matter Change scale (ARWMC).
• Quantitative assessment of cortical HPτ and Aβ burden (using AT8 and 4G8 immunoreactivity) and WM SVD severity (sclerotic index).
• Statistical comparison of ARWMC scores with HPτ, Aβ, and SVD markers in AD cases versus controls.

Main Results:

• AD cases showed higher HPτ, Aβ, and WMH scores than controls; SVD severity was similar.
• WMH scores correlated with HPτ, Aβ, and SVD markers.
• Linear regression identified cortical HPτ burden as the sole independent predictor of WMH severity.

Conclusions:

• Elevated cortical HPτ burden independently predicts WMH severity, highlighting its role in white matter damage pathogenesis.
• WMH in AD patients may reflect underlying cortical AD pathology, not solely SVD.
• Further research is needed to understand WMH pathogenesis and its potential as a biomarker for AD-associated pathology.