Liu P, Smith BR, Huang ES, Mahesh A, Vonsattel JPG, Petersen AJ, Gomez-Pastor R, Ashe KH. A Soluble Truncated Tau Species Related to Cognitive Dysfunction and Caspase-2 Is Elevated in the Brain of Huntington’s Disease Patients. Acta Neuropathologica Communications. 2019;7:1-13. PMID: 31358058. DOI: 10.1186/s40478-019-0764-9.
Summary
This study investigated whether Δtau314 is elevated in Huntington’s disease, a neurodegenerative disorder not traditionally classified as a primary tauopathy. The authors found increased levels of the soluble caspase-2-related tau fragment in brain tissue from patients with Huntington’s disease and linked these changes to cognitive dysfunction. The findings suggest that abnormal tau processing may contribute to cognitive impairment in Huntington’s disease and that caspase-2-mediated tau cleavage may be relevant across mechanistically diverse neurodegenerative disorders.
Key Findings
- Δtau314 was elevated in Huntington’s disease brain tissue.
- The tau fragment was associated with cognitive dysfunction.
- Findings extended caspase-2/tau biology beyond classical tauopathies.
- Results support the cross-disease relevance of soluble tau toxicity.
Impact on the Caspase-2/Tau Program
This paper broadened the disease rationale for targeting caspase-2-mediated tau cleavage. It suggests that caspase-2 inhibitors may have potential in multiple disorders with cognitive impairment.