Cellular models for tau filament assembly.

Filamentous inclusions made of phosphorylated tau constitute a neuropathologic hallmark of Alzheimer's disease and related disorders. Because abnormal accumulation of tau correlates with the decline in cognitive function, it is conceivable that effective intervention at the early stage of tau filament assembly could impede the progression of these neurodegnerative diseases. Cellular models recapitulating the tau aberration are useful for screening and identifying compounds that are capable of interfering with tau aggregation in a cost-effective manner. To develop such cell culture models, we have established from human neuroglioma [H4] and neuronal [BE(2)-M17D] cells conditional transfectants whose transgenic expression of wild-type or mutant tau via inducible expression mechanisms leads to tau aggregation and filament assembly.