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Hereditary Pick's disease with the G272V tau mutation shows predominant three-repeat tau pathology
- Source :
- Bronner, I F, ter Meulen, B C, Azmani, A, Severijnen, L A, Willemsen, R, Kamphorst, W, Ravid, R, Heutink, P & van Swieten, J C 2005, ' Hereditary Pick's disease with the G272V tau mutation shows predominant three-repeat tau pathology ', Brain, vol. 128, no. Pt 11, pp. 2645-2653 . https://doi.org/10.1093/brain/awh591, Brain, 128, 2645-2653. Oxford University Press, Brain, 128(Pt 11), 2645-2653. Oxford University Press
- Publication Year :
- 2005
- Publisher :
- Oxford University Press, 2005.
-
Abstract
- Frontotemporal dementia and parkinsonism linked to chromosome 17 have been associated with mutations in the microtubule associated protein tau (MAPT or tau) gene. This disorder is characterized by a large spectrum of neuronal and glial tau lesions in different brain regions. Pick bodies were found in a family with hereditary Pick’s disease with the G272V mutation and in several families with other tau mutations in exons 9 and 11–13. The biochemical composition of Pick bodies varies between these mutations. Until recently, no detailed biochemical characterization of G272V brain material was done owing to unavailability of fresh frozen brain material. We now report a detailed study using the immunohistochemistry, western blots and electron microscopy of two brains with the G272V mutation that recently became available. Both brains showed severe neuronal loss in the temporal cortex, whereas in the frontal cortex the loss was less; and abundant Pick bodies in the dentate gyrus of the hippocampus, and caudate nucleus. The Pick bodies consisted exclusively of threerepeat (3R) isoforms, as was demonstrated by isoform-specific antibodies and supported by western blot analysis of sarkosyl-insoluble tau. These observations confirm that this family diagnosed with hereditary Pick disease meets all the criteria for this condition, including the presence of Pick bodies that are unphosphorylated at Ser 262 and contain twisted filaments with long periodicity consisting only of 3R tau.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Blotting, Western
DNA Mutational Analysis
Caudate nucleus
Hippocampus
Nerve Tissue Proteins
tau Proteins
Biology
medicine.disease_cause
Frontotemporal dementia and parkinsonism linked to chromosome 17
Degenerative disease
Pick Disease of the Brain
medicine
Humans
Temporal cortex
Mutation
Dentate gyrus
Middle Aged
medicine.disease
Frontal Lobe
Pedigree
Haplotypes
Pick's disease
Female
Neurology (clinical)
Chromosomes, Human, Pair 17
Subjects
Details
- ISSN :
- 14602156 and 00068950
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Brain
- Accession number :
- edsair.doi.dedup.....8cdbfaff0fe0fc91a08f646c20e66bc7