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Cellular and regional vulnerability in frontotemporal tauopathies
Shelley L Forrest1, Jillian J Kril1, Glenda M Halliday2
1Charles Perkins Centre and Discipline of Pathology, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Acta Neuropathologica
|June 17, 2019
Summary
Frontotemporal tauopathies involve abnormal tau protein deposits with distinct pathologies. Understanding these subtypes, their genetic links, and spread is crucial for developing targeted therapies and biomarkers.
Area of Science:
- Neuroscience
- Neuropathology
- Genetics
Background:
- Frontotemporal tauopathies are characterized by abnormal tau protein aggregates, presenting diverse pathologies like neuronal and glial inclusions.
- While tau aggregates are central, the role of glial cells in tau production and pathology remains under investigation.
Purpose of the Study:
- To review the differentiating features, clinicopathological correlations, and genetic predispositions of frontotemporal tauopathies.
- To explore neuroanatomical selectivity, disease spread patterns, and contributing cellular/molecular changes in these conditions.
- To highlight the importance of distinct pathological subtypes for understanding disease mechanisms and therapeutic development.
Main Methods:
- Review of existing literature on frontotemporal tauopathies, focusing on pathology, genetics, and clinical correlations.
- Analysis of neuroanatomical distribution, disease spread patterns, and cellular/molecular changes.
- Examination of genetic associations with specific tau pathologies and neuroinflammatory mechanisms.
Main Results:
- Clinical phenotypes correlate more with the degenerating brain region than the specific tau pathology type.
- Specific tau pathologies are linked to distinct regions of the MAPT gene and novel risk genes.
- 4-repeat tauopathies show different spreading patterns compared to neuronal pathologies, with evidence of neuroinflammation.
Conclusions:
- Distinct frontotemporal tauopathy subtypes differ in affected cell types, morphology, and distribution, crucial for understanding disease mechanisms.
- Targeted therapies and biomarkers are needed, emphasizing the importance of differentiating these subtypes.
- Future research should address regional and cellular vulnerabilities to advance therapeutic strategies.
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