title: Alzheimer neurofibrillary tangles contain 2.1 nm filaments structurally identical to the microtubule-associated protein tau: a high-resolution transmission electron microscope study of tangles and senile plaque core amyloid.
abstract: Alzheimer neurofibrillary tangles (NFT) and senile plaque core amyloid (SPCA) isolated from the brain of patients with Alzheimer's disease were freeze-dried and replicated with a new platinum-carbon (Pt-C) vertical deposition method for high-resolution transmission electron microscopy (TEM). The resolution of this vertical Pt-C replication method is superior to either of the more conventional 20 degrees rotary replication or 45 degrees unidirectional replication methods and is dependent on the Pt-C film thickness coating the specimen. The paired helical filaments (PHF) observed within the tangles were right-handed helices with a fairly regular twist period averaging 79.3 +/- 5.9 nm and a fairly regular maximum width averaging 14.9 +/- 1.0 nm. The PHF regions of minimum width were not regular and fell into three size categories: 2.4 +/- 0.3 nm, 4.9 +/- 0.6 nm and 9.6 +/- 1.4 nm. In addition to the PHF found in the tangles, a new filament was found within all the tangles. These 2.1 +/- 0.2 nm diameter filaments were triple-stranded left helices with 1.0 +/- 0.2 nm diameter strands with a structure identical to bovine tau. Like bovine tau polymer a number of filaments (130 nm to 238 nm) were longer than a fully stretched tau monomer of 96 nm. Images of neuritic senile plaque core amyloid (SPCA) showed that amyloid had a more solid appearance than the NFT and its branched filament structures were unlike the approximately 2.1 nm diameter filaments or the PHF found in NFT.
authors.affiliation: Department of Biological Sciences, Dartmouth College, Hanover, NH 03755.
authors.forename: G C
authors.initials: GC
authors.lastname: Ruben
authors.forename: K
authors.initials: K
authors.lastname: Iqbal
authors.forename: H M
authors.initials: HM
authors.lastname: Wisniewski
authors.forename: J E
authors.initials: JE
authors.lastname: Johnson
authors.forename: I
authors.initials: I
authors.lastname: Grundke-Iqbal
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism / Q000648:ultrastructure*; D001921:Brain / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005612:Freeze Drying; D006801:Humans; D007382:Intermediate Filaments / Q000648:ultrastructure*; D008854:Microscopy, Electron; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000648:ultrastructure*; D013194:Staining and Labeling; D016875:tau Proteins / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D000682:Amyloid; D016875:tau Proteins