Relationship between cortical iron and tau aggregation in Alzheimer's disease

Research output: Contribution to journalArticle

Abstract

A growing body of evidence suggests that the dysregulation of neuronal iron may play a critical role in Alzheimer's disease. Recent MRI studies have established a relationship between iron accumulation and amyloid-β aggregation. The present study provides further insight demonstrating a relationship between iron and tau accumulation using magnetic resonance-based quantitative susceptibility mapping and tau-PET in n = 236 subjects with amyloid-β pathology (from the Swedish BioFINDER-2 study). Both voxel-wise and regional analyses showed a consistent association between differences in bulk magnetic susceptibility, which can be primarily ascribed to an increase in iron content, and tau-PET signal in regions known to be affected in Alzheimer's disease. Subsequent analyses revealed that quantitative susceptibility specifically mediates the relationship between tau-PET and cortical atrophy measures, thus suggesting a modulatory effect of iron burden on the disease process. We also found evidence suggesting the relationship between quantitative susceptibility and tau-PET is stronger in younger participants (age ≤ 65). Together, these results provide in vivo evidence of an association between iron deposition and both tau aggregation and neurodegeneration, which help advance our understanding of the role of iron dysregulation in the Alzheimer's disease aetiology.

Details

Authors
Organisations
External organisations
  • Skåne University Hospital
  • University of Pennsylvania
  • Tenoke Ltd.
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
  • Neurosciences

Keywords

  • Alzheimer’s disease, iron, quantitative susceptibility mapping, tau, tau-PET
Original languageEnglish
Pages (from-to)1341-1349
Number of pages9
JournalBrain : a journal of neurology
Volume143
Issue number5
Publication statusPublished - 2020 May
Publication categoryResearch
Peer-reviewedYes