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Tau Pathology in a Family with Dementia and a P301L Mutation in Tau
Abstract
Familial forms of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) have recently been associated with coding region and intronic mutations in the tau gene. Here we report our findings on 2 affected siblings from a family with early-onset dementia, characterized by extensive tau pathology and a Pro to Leu mutation at codon 301 of tau. The proband, a 55-year-old woman, and her 63-year-old brother died after a progressive dementing illness clinically diagnosed as Alzheimer disease. Their mother, 2 sisters, maternal aunt and uncle, and several cousins were also affected. Autopsy in both cases revealed frontotemporal atrophy and degeneration of basal ganglia and substantia nigra. Sequencing of exon 10 of the tau gene revealed a C to T transition at codon 301, resulting in a Pro to Leu substitution. Widespread neuronal and glial inclusions, neuropil threads, and astrocytic plaques similar to those seen in corticobasal degeneration were labeled with a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes spanning the entire tau sequence. Isolated tau filaments had the morphology of narrow twisted ribbons. Sarkosyl-insoluble tau exhibited 2 major bands of 64 and 68 kDa and a minor 72 kDa band, similar to the pattern seen in a familial tauopathy associated with an intronic tau mutation. These pathological tau bands predominantly contained the subset of tau isoforms with 4 microtubule-binding repeats selectively affected b…
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MAPT mutations such as MAPT R406W can cause familial FTLD-tau.
“MAPT mutations such as MAPT R406W can cause familial frontotemporal lobar degeneration with tau (FTLD-tau)1–3.”
From GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau (2025) · cites this paper as [1]
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GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau
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Metadata
- Authors
- Mirra, S. S., Murrell, J. R., Gearing, M., Spillantini, M. G., Goedert, M., Crowther, R. A., Levey, A. I., Jones, R., Green, J., Shoffner, J. M., Wainer, B. H., Schmidt, M. L., Trojanowski, J. Q., & Ghetti, B.
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-04
- Volume
- 58
- Issue
- 4
- Pages
- 335-345
- ISSN
- 0022-3069
- Cited by
- 163
- References
- 0
- Language
- en
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