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Information about how these conditions interact, or about the temporal order in which they appear, is lacking. This study investigated if, and when, iron\u2010related changes occur in the R6\/2 transgenic mouse model of HD and compared the results with those from HD patients. Relative to wild\u2010type mice, R6\/2 mice had increased immunostaining for ferritin, an iron storage protein, in the striatum beginning at 2\u20134 weeks postnatal and in cortex and hippocampus starting at 5\u20137 weeks. The ferritin staining was found primarily in microglia, and became more pronounced as the mice matured. Ferritin\u2010labeled microglia in R6\/2 mice appeared dystrophic in that they had thick, twisted processes with cytoplasmic breaks; some of these cells also contained the mutant huntingtin protein. Brains from HD patients (Vonsattel grades 0\u20134) also had increased numbers of ferritin\u2010containing microglia, some of which were dystrophic. The cells were positive for Perl's stain, indicating that they contained abnormally high levels of iron. These results provide the first evidence that perturbations to iron metabolism in HD are predominately associated with microglia and occur early enough to be important contributors to HD progression. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20526","type":"journal-article","created":{"date-parts":[[2007,6,5]],"date-time":"2007-06-05T13:46:42Z","timestamp":1181051202000},"page":"1074-1084","source":"Crossref","is-referenced-by-count":258,"title":["Ferritin accumulation in dystrophic microglia is an early event in the development of Huntington's disease"],"prefix":"10.1002","volume":"55","author":[{"given":"Danielle 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