Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

New Insight into Alzheimer's Disease via Caspase 3-cleaved Tau: Pathogenic Role in Tau Oligomer Formation and Memory Deficits

Young Doo Kima, Jisu Parka and Yong Keun Jung

Alzheimer’s disease (AD) is the most common and leading cause of dementia. AD has two different pathological hallmarks, extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFT). NFTs consist of abnormally modified tau protein that forms protein aggregates. Tau protein aggregates are prevalently observed as disease progresses and are believed to cause neuronal dysfunction. The caspase-3 cleaved form of tau, TauC3, is generated in cultured neurons under stress and is found in the brains of patients with AD in the early stages of disease when patients are asymptomatic. TauC3 accelerates tau oligomerization in vitro and in vivo, and induces neuronal degeneration. Moreover, the neuronal expression of TauC3 in transgenic mice causes memory deficits at a young age, which is concomitant with the appearance of tau oligomers. The removal of TauC3-containing oligomers and aggregates using drug treatment improves both memory and synaptic function. These findings demonstrate that TauC3 is critical for the formation of tau oligomers and small aggregates and may ultimately play a role in the rapid memory impairments observed in AD. Overall, TauC3 may represent a new therapeutic target for the prevention of AD.