Cerebellar Mild Iron Accumulation in a Subset of FMR1 Premutation Carriers with FXTAS.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene. Iron is essential for many facets of cell metabolism in the brain but when altered is likely to contribute to the development of neurodegenerative diseases. We previously reported that iron accumulates in the choroid plexus and the putamen in FXTAS and that the level and distribution of key iron-binding proteins are also altered, suggesting a potential alteration of iron metabolism in the brain. Here, we hypothesize that iron metabolism is also altered in the FXTAS cerebellum. To test this hypothesis, we used cerebellum samples collected from FXTAS and control subjects and measured the amount of iron contained within the cerebellar cortex and dentate nucleus. We found that the number of iron deposits increased in the cerebellum only in a subset of cases of FXTAS. This accumulation is likely to be mediated by factors other than or in addition to CGG-repeat coupled pathology. Thus, iron deposition in the cerebellum cannot be used as a hallmark of FXTAS pathogenesis.
Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Hailee
H
Rogers
Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Jeanelle
J
Ariza
Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Angela
A
Monterrubio
MIND Institute, UC Davis Medical Center, Sacramento, CA, USA.|Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA, USA.
Paul
P
Hagerman
Department of Pathology and Laboratory Medicine, UC Davis School of Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA. vmartinezcerdeno@ucdavis.edu.|MIND Institute, UC Davis Medical Center, Sacramento, CA, USA. vmartinezcerdeno@ucdavis.edu.
Verónica
V
Martínez-Cerdeño
D000368:Aged; D000369:Aged, 80 and over; D001259:Ataxia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014202:Tremor / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D019680:Trinucleotide Repeat Expansion
D051860:Fragile X Messenger Ribonucleoprotein 1; D007501:Iron; C497683:FMR1 protein, human
FXTAS; Fragile X tremor ataxia; Purkinje cells; cerebellum; human; iron