Solving the insoluble.

Dissection of neurofibrillary tangles has been confounded by the insolubility of their fibers. While the majority of biochemical studies have considered tau filaments equivalent to neurofibrillary tangles, they forget that the former are soluble and the latter completely resistant to solvents. What, then, accounts for the insolubility of neurofibrillary tangles while tau filaments are soluble? Investigation of these distinctions played a critical role in our findings on proteolytic abnormalities and oxidative stress.