THE ORGANIZATION OF THE MICROTUBULE ASSOCIATED PROTEIN-TAU IN ALZHEIMER PAIRED HELICAL FILAMENTS

The structural relationship of the microtubule associated protein tau to paired helical filaments (PHF) was examined by high resolution transmission electron microscopy (TEM) without treatment with any chemical fixatives. Neurofibrillary tangles (NFT) were isolated in the absence of detergent from Alzheimer diseased brains, were freeze-dried, and were vertically platinum-carbon replicated for TEM. The PHF we observed made one helical turn (L) in 74 +/- 8.5 nm and had a wide region (W) of 14.8 +/- 0.6 nm similar to PHF previously modeled with a periodic morphology. The PHF thin region (T) measured approximately 2.4 nm, approximately 4.9 nm, approximately 7.4 nm and approximately 9.7 nm and the most often observed width was approximately 2.4 nm. No surface features regularly divide the PHF into two filaments. Morphologically the PHF are thin helical ribbons with an often observed thickness of approximately 2.4 nm. At high magnification, approximately 1.0 nm and some approximately 0.4 nm strands identical to normal and denatured tau monomer covered PHF surfaces and were aggregated in non-periodic fashion. Bovine tau polymer approximately 2.1 nm diameter filaments, trapped on a filter, were partially heat denatured and showed some of the morphological features of PHF.