This method for inducing tau to form polymers hinges on the discovery that the addition of free fatty acids to solutions of recombinant human tau protein can greatly enhance this process (Wilson & Binder, 1997).  One of the major polyunsaturated fatty acids found in mammalian brain, Arachidonic Acid works particularly well for this induction.

    The filaments that are formed have been found to be similar to filaments found in Alzheimer's disease immunologically, morphologically, and structurally (King et. al., 1999).

    We have also developed a new assay for monitoring this process in vitro.  This method is similar to the turbidimetric measurement of polymers in solution, but instead of measuring the decrease in the amount of transmitted light, we measure the increase in the light scattered by polymers in solution (Gamblin et. al., 2000).

    Using these procedures for inducing and monitoring tau polymerization, we have made several discoveries about the properties of the tau molecule:

• Isoform differences:  The different exons that are alternatively spliced out of the tau molecule can affect tau's polymerization.
• Point mutations:  Different point mutations in the tau protein that are found in a class of neurodegenerative diseases known as FTDP-17 (frontotemporal dementia with Parkensonism linked to chromosome-17) can greatly alter the polymerization of the tau molecule.
• Structural modifications:  Site-specific phosphorylation and C-terminal truncation of the tau molecule that is observed in Alzheimer's disease can lead to increased tau polymerization.
• Oxidation:  Different oxidative conditions can lead to altered tau polymerization.