A Majority of FXTAS Cases Present with Intranuclear Inclusions Within Purkinje Cells.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder that affects carriers of a FMR1 premutation. Symptoms include cerebellar ataxia, tremor, and cognitive deficits. The most characteristic pathology of FXTAS is the presence of eosinophilic ubiquitin-positive intranuclear inclusions in neurons and astrocytes throughout the nervous system and non-nervous tissues. Inclusions are present in neurons throughout the brain but are widely believed not to be present in the Purkinje cells (PCs) of the cerebellum. However, we analyzed 26 postmortem cases of FXTAS and demonstrated that 65 % of cases presented with inclusions within PCs of the cerebellum. We determined that the presence or absence of inclusions in PCs is correlated with age and that those cases with PC inclusions were overall 11 years older than those with no PC inclusions. Half of the cases with PCs with inclusions presented with twin nuclear inclusions. This novel finding demonstrating the presence of inclusions within PCs provides an insight into the understanding of the FXTAS motor symptoms and provides a novel target for the development of therapeutic strategies.
Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, UC Davis School of Medicine, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Jeanelle
J
Ariza
Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, UC Davis School of Medicine, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Hailee
H
Rogers
Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, UC Davis School of Medicine, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Angela
A
Monterrubio
Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, UC Davis School of Medicine, 2425 Stockton Boulevard, Sacramento, CA, 95817, USA.
Adriana
A
Reyes-Miranda
MIND Institute, UC Davis Medical Center, Sacramento, CA, USA.|Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA, USA.
Paul J
PJ
Hagerman
Department of Pathology and Laboratory Medicine, Institute for Pediatric Regenerative Medicine and Shriners Hospitals for Children of Northern California, UC Davis School of Medicine, 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
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D001259:Ataxia / Q000473:pathology*; D005260:Female; D005600:Fragile X Syndrome / Q000473:pathology*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011689:Purkinje Cells / Q000473:pathology*; D014202:Tremor / Q000473:pathology*
Cerebellum; FRMP; FXTAS; Purkinje cells; Ubiquitin