Amyloid and tau pathologies are drivers of white matter damage in aging and Alzheimer’s disease

Introduction

Alzheimer’s disease (AD) is typically characterized by amyloid-βeta (Aβ) plaques and neurofibrillary tau tangle buildup in the brain [1–3].
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Another common pathological markers observed in the aging brain is white matter hyperintensities (WMHs)[4].
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WMHs are hallmarks of cerebral small vessel disease (CSVD) and are also associated with an increased risk of cognitive decline and development of dementia[5–6].
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What remains less clear is whether cerebrovascular pathology occurs before, after, or concurrently with the progression of Aβ and tau pathology, and whether these temporal relationships differ across brain regions.
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OBJECTIVE: This study investigated the temporal and regional associations between PET measures ofAβand tau pathology and WMH burden in older adults.

Methods

Linear models were used to i) assess associations between baseline regional WMH and Aβ and tau pathology, and ii) examine whether baseline pathology in one measure was associated with change in the other measure over two years.

Conclusiuon

Amyloid and tau pathologies drive subsequent WMH accumulation rather than the reverse.
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The regional specificity of the proteinopathyeffects on WMH accumulation further supports the notion that posterior WMHs and their progression are likely linked to accumulation of AD rather than vascular pathologies.