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An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
The tau S305S mutation causes frontotemporal dementia with parkinsonism
L Skoglund1, M Viitanen, H Kalimo
1Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. lena.skoglund@pubcare.uu.se
European Journal of Neurology
|December 21, 2007
Summary
Mutations in the tau gene cause varied neurological disorders. This study identifies a new frontotemporal dementia phenotype for the tau S305S mutation, linked to altered tau protein levels.
Area of Science:
- Neuroscience
- Genetics
- Pathology
Background:
- Familial mutations in the tau gene are associated with heterogeneous clinical presentations, including frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP).
- The tau S305S mutation was previously linked to PSP, but its full clinical spectrum remains under investigation.
Observation:
- Three family members with the tau S305S mutation presented with personality/behavioral changes, cognitive decline, and late-onset, levodopa-resistant parkinsonism.
- Autopsy of one case revealed frontal and temporal lobe degeneration with widespread tau pathology in neurons and glial cells.
- Analysis of brain tissue showed a shift in tau isoforms, with decreased three-repeat (3R) tau and increased four-repeat (4R) tau.
Findings:
- The S305S mutation is associated with a frontotemporal dementia with parkinsonism phenotype, expanding the known clinical spectrum.
- The mutation influences tau splicing, leading to an overproduction of 4R tau, a key pathological hallmark in tauopathies.
- Pathological findings confirm significant neurodegeneration and abnormal tau accumulation in affected brain regions.
Implications:
- These findings highlight the significant clinical and pathological variability associated with tau gene mutations.
- Understanding the impact of specific tau mutations on tau isoform ratios is crucial for diagnosing and potentially treating tauopathies.
- This research contributes to the broader understanding of FTD and related neurodegenerative disorders linked to tau pathology.
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