title: Iron in Frontotemporal Lobar Degeneration: A New Subcortical Pathological Pathway?
abstract: BACKGROUND
  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.
authors.affiliation: Neurology Unit, Centre for Ageing Brain and Neurodegenerative Disorders, Spedali Civili, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gazzina
authors.forename: Enrico
authors.initials: E
authors.lastname: Premi
authors.forename: Isabella
authors.initials: I
authors.lastname: Zanella
authors.forename: Giorgio
authors.initials: G
authors.lastname: Biasiotto
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Maura
authors.initials: M
authors.lastname: Cosseddu
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.forename: Roberto
authors.initials: R
authors.lastname: Gasparotti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D005787:Gene Frequency; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D000071020:Hemochromatosis Protein / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D010865:Pilot Projects; D011110:Polymorphism, Genetic
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D007501:Iron