Smith BR, Nelson KM, Kemper LJ, Leinonen-Wright K, Petersen A, Keene CD, Ashe KH. A Soluble Tau Fragment Generated by Caspase-2 Is Associated with Dementia in Lewy Body Disease. Acta Neuropathologica Communications. 2019;7:1-9. PMID: 31362787. DOI: 10.1186/s40478-019-0765-8.
Summary
This study examined whether Δtau314 is associated with dementia in Lewy body disease. Using human brain samples, the authors found elevated levels of the caspase-2-generated tau fragment in Lewy body disease cases compared with non-demented Parkinson’s disease controls. The findings suggest that Δtau314 may contribute to cognitive impairment across neurodegenerative diseases beyond Alzheimer’s disease. The work also supports the possibility that caspase-2-mediated tau cleavage represents a shared mechanism of synaptic dysfunction in multiple dementias.
Key Findings
- Δtau314 was elevated in Lewy body disease with dementia.
- The comparison excluded confounding factors related to Alzheimer’s pathology.
- Soluble tau changes were linked to cognitive status.
- Results suggested broader relevance beyond Alzheimer’s disease.
Impact on the Caspase-2/Tau Program
This paper expanded the therapeutic relevance of caspase-2 beyond Alzheimer’s disease. It supports a broader dementia strategy centered on synaptotoxic tau fragments.