You should consider that recent results point out that not the aggregates but oligomers are the toxic species. Maybe, your tau aggregates too fast while excess oligomeric species are cleared by the proteasome. You could try targeting this pathway.

Good point! I should read papers describing soluble tau oligomers...

Thank you David!

Thanks! I will try the methods described in the paper.

I have worked on a different protein beta2microglobulin and published a paper in Journal of Biological Chemistry.

http://www.researchgate.net/profile/Abdullah_Sultan3/

This protein is not cytotoxic in its native form even at 10 fold higher concentration... but when I make the amyloid fibrils of beta2 microglobulin and add to cells . the protein results in a 50% reduction in viability of macrophage cells.

Also this was specific to macrophage cell line and some other cell lines (ie many other cell lines still did not exhibited a decrease in viability).

I believe that - To make your protein tau cytotoxic ...you need to somehow convert it into toxic oligomers or fibrils ... and mere overexpression in cells will not help.

Also some proteins like synuclein are known to form oligomers and fibrils inside cells when a combination is done -- 1) overexpressed and 2) the cells are treated with stress inducing drug eg. oliogomycin (to induce proteasomal stress in case of syn in neuroblastoma cell lines).

Although i did not answer your question.. but hope this helps and good luck.

I recall during the 1990s that many attempts were made to model tau toxicity using WT tau overexpression in cell lines. None of these worked unless over expression was combined with toxic manipulations (such as treatment with okadaic acid). We tried over expressing human tau in giant lamprey neurons in situ via plasmid microinjection (Hall et. al.1997 PNAS) and had no problem getting tau-specific neurodegeneration. Shortly after this, WT tau overexpression by itself was found to be effective in inducing some neurofibrillary pathology in mice (Ishihara et al 1999, Neuron).

I've always thought that this carried with it an important lesson - that the differentiated neuronal state plays an important (and mostly ignored) role in tau toxicity.

This doesn't appear to be the case for A beta.

Over expression of tau proteins merely not affects apoptotic cell death but It should be hyperphosphorylation of tau. It will come if you will try with hyperphosphorylated tau protein to induce cell death.

As many suggested above, mere overexpression of Tau in cells will not cause apoptosis. But it could cause some other toxic effects which one need to focus on.  If you would like to study only the apoptotic pathway induced by Tau aggregation in cells, one should use mutant Tau, such as

If you would like to study only the apoptotic pathway induced by Tau aggregation in cells, the following criteria must be met to my knowledge.

1.one should use mutant Tau, such as delka K280, P301L etc. 

2. The fulllength Tau even with the mutation does not form ThS positive aggregates (which are considered as pathological aggregates - presume to contain filaments). Therefore one should use the repeat domain of Tau alone to induce the aggregation inside the cells. In that

In that case, one could definitely observe ThS positive aggregates, cell death and other toxic effects.

3. please find the below the link for the article where you might get the information you want.

Article Time course of Tau toxicity and pharmacological prevention i...

Article Extracellular low-n oligomers of tau cause selective synapto...

Tau hypothesis:

Tau hypothesis is a predominant pathological concomitant to Alzheimer’s disease. Although several ethological studies have addressed the complexity and consequence of these hallmarks and very little is known about this corner of neuroscience. In the year of 1985, J.P. Brion and André Delacourte were the first to suggest that tau might be the main component of NFTs. Soon after, in 1988, Michel Goedert and collaborators cloned the cDNA of PHF-tau. Every neuron has a cytoskeleton, an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. Microtubules are made-up of tubulin monomers with the help of tau protein. In AD patients brain, the τ -protein undergo hyperphosphorylated and it loses capacity of binding to microtubules. The unbounded τ –protein was aggregates together and forms insoluble paired-helical filaments (PHFs). Finally these deposits of NFT are the responsible for the neuronal cells death.