Iron in Frontotemporal Lobar Degeneration: A New Subcortical Pathological Pathway?

Stefano Gazzina, Enrico Premi, Isabella Zanella, Giorgio Biasiotto, Silvana Archetti, Maura Cosseddu, Elio Scarpini, Daniela Galimberti, Maria Serpente, Roberto Gasparotti, Alessandro Padovani, Barbara Borroni

Research output: Contribution to journalArticlepeer-review


Introduction: Brain iron homeostasis dysregulation has been widely related to neurodegeneration. In particular, human haemochromatosis protein (HFE) is involved in iron metabolism, and HFE H63D polymorphism has been related to the risk of amyotrophic lateral sclerosis and Alzheimer's disease. Recently, iron accumulation in the basal ganglia of frontotemporal lobar degeneration (FTLD) patients has been described. Objective: To explore the relationship between HFE genetic variation and demographic, clinical and imaging characteristics in a large cohort of FTLD patients. Methods: A total of 110 FTLD patients underwent neuropsychological and imaging evaluation and blood sampling for HFE polymorphism determination. HFE H63D polymorphism was considered in the present study. Two imaging approaches were applied to evaluate the effect of HFE genetic variation on brain atrophy, namely voxel-based morphometry and region of interest-based probabilistic approach (SPM8; Wellcome Trust Centre for Neuroimaging). Results: FTLD patients carrying the D* genotype (H/D or D/D) showed greater atrophy in the basal ganglia, bilaterally, compared to H/H carriers (x, y, z: -22, -4, 0; T = 3.45; cluster size: 33 voxels, x, y, z: 24, 4, -2; T = 3.38; cluster size: 36 voxels). The former group had even more pronounced behavioural symptoms, as defined by the Frontal Behavioural Inventory total scores. Conclusions: Our data suggest that H63D polymorphism could represent a disease-modifying gene in FTLD, fostering iron deposition in the basal ganglia. This suggests a new possible mechanism of FTLD-associated neurodegeneration.

Original languageEnglish
Pages (from-to)172-178
Number of pages7
JournalNeurodegenerative Diseases
Issue number3-4
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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