title: The role of iron in gray matter degeneration in Huntington's disease: a magnetic resonance imaging study.
abstract: In Huntington's disease, iron accumulation in basal ganglia accompanies neuronal loss. However, if iron content changes with disease progression and how it relates to gray matter atrophy is not clear yet. We explored iron content in basal ganglia and cortex and its relationship with gray matter volume in 77 mutation carriers [19 presymptomatic, 8 with soft symptoms (SS), and 50 early-stage patients) and 73 matched-controls by T2*relaxometry and T1-weighted imaging on a 3T scanner. The ANCOVA model showed that iron accumulates in the caudate in presymptomatic subjects (P = 0.004) and remains relatively stable along disease stages in this nucleus; while increases in putamen and globus pallidus (P < 0.05). Volume instead decreases in basal ganglia, starting from the caudate (P < 0.0001) and extending to the putamen and globus pallidus (P ≤ 0.001). The longer the disease duration and the higher the CAG repeats, the higher the iron accumulation and the smaller the volume. In the cortex, iron decreases in parieto-occipital areas in SS (P < 0.027); extending to premotor and parieto-temporo-occipital areas in patients (P < 0.003); while volume declines in frontoparietal and temporal areas in presymptomatic (P < 0.023) and SS (P < 0.045), and extends throughout the cortex, with the exception of anterior frontal regions, in patients (P < 0.023). There is an inverse correlation between volume and iron levels in putamen, globus pallidus and the anterior cingulate; and a direct correlation in cortical structures (SMA-sensoriomotor and temporo-occipital). Iron homeostasis is affected in the disease; however, there appear to be differences in the role played by iron in basal ganglia and in cortex.
authors.affiliation: Department of Radiology, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Castañeda
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Squitieri
authors.forename: Margherita
authors.initials: M
authors.lastname: Di Paola
authors.forename: Michael
authors.initials: M
authors.lastname: Dayan
authors.forename: Martina
authors.initials: M
authors.lastname: Petrollini
authors.forename: Umberto
authors.initials: U
authors.lastname: Sabatini
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000150:complications* / Q000235:genetics; D021621:Imaging, Three-Dimensional; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology*; D012720:Severity of Illness Index; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D007501:Iron
keywords: Huntington's disease; MRI; iron; multimodal; neuronal loss