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

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T1 - Relationship between cortical iron and tau aggregation in Alzheimer's disease

AU - Spotorno, Nicola

AU - Acosta-Cabronero, Julio

AU - Stomrud, Erik

AU - Lampinen, Björn

AU - Strandberg, Olof T.

AU - van Westen, Danielle

AU - Hansson, Oskar

PY - 2020/5

Y1 - 2020/5

N2 - 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.

AB - 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.

KW - Alzheimer’s disease

KW - iron

KW - quantitative susceptibility mapping

KW - tau

KW - tau-PET

UR - http://www.scopus.com/inward/record.url?scp=85085155422&partnerID=8YFLogxK

U2 - 10.1093/brain/awaa089

DO - 10.1093/brain/awaa089

M3 - Article

C2 - 32330946

AN - SCOPUS:85085155422

VL - 143

SP - 1341

EP - 1349

JO - Brain

JF - Brain

SN - 1460-2156

IS - 5

ER -