Frontotemporal Dementia and Corticobasal Degeneration in a Family with a P301S Mutation in Tau
Abstract
The tau gene has been found to be the locus of dementia with rigidity linked to chromosome 17. Exonic and intronic mutations have been described in a number of families. Here we describe a P301S mutation in exon 10 of the tau gene in a new family. Two members of this family were affected. One individual presented with frontotemporal dementia, whereas his son has corticobasal degeneration, demonstrating that the same primary gene defect in tau can lead to 2 distinct clinical phenotypes. Both individuals developed rapidly progressive disease in the third decade. Neuropathologically, the father presented with an extensive filamentous pathology made of hyperphosphorylated tau protein. Biochemically, recombinant tau protein with the P301S mutation showed a greatly reduced ability to promote microtubule assembly.
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Several tau mutations linked to FTDP-17 have been identified.
“Several tau mutations linked to FTDP-17 have been identified (2 -7)”
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Self-citation
- Authors
- Bugiani, O., Murrell, J. R., Giaccone, G., Hasegawa, M., Ghigo, G., Tabaton, M., Morbin, M., Primavera, A., Carella, F., Solaro, C., Grisoli, M., Savoiardo, M., Spillantini, M. G., Tagliavini, F., Goedert, M., & Ghetti, B.
- Affiliations
- Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
- Indiana University Indianapolis (US)
- MRC Laboratory of Molecular Biology (GB)
- University of Genoa (IT)
- University of Cambridge (GB)
- Corresponding author
- Bugiani, Orso
- ORCID
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-06
- Volume
- 58
- Issue
- 6
- Pages
- 667-677
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W1992973287
- Cited by
- 450
- References
- 0
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 14 · 2023: 14 · 2022: 20 · 2021: 21 · 2020: 15 · 2019: 13 · 2018: 12 · 2017: 11 · 2016: 11 · 2015: 18 · 2014: 12 · 2013: 10 · 2012: 8
- FWCI
- 15.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ns014426-18, 5r01ns037431-03)
- National Institute on Aging (AG 10133, P30AG010133)
- National Institute of Neurological Disorders and Stroke (NS-14426, NS37431)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- tau gene, frontotemporal dementia, corticobasal degeneration, familial dementia, hyperphosphorylated tau, tau filaments, microtubule assembly, chromosome 17, genotype-phenotype correlation
- MeSH terms
- Adult, Basal Ganglia Diseases, Cerebral Cortex, Dementia, DNA, Family Health, Frontal Lobe, Humans, Immunohistochemistry, Magnetic Resonance Imaging, Microtubules, Middle Aged, Mutation, Nerve Degeneration, Pedigree, Temporal Lobe, tau Proteins
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