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.
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.
Ruben
G C
GC
Department of Biological Sciences, Dartmouth College, Hanover, NH 03755.
Iqbal
K
K
Wisniewski
H M
HM
Johnson
J E
JE
Grundke-Iqbal
I
I
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*
D000682:Amyloid; D016875:tau Proteins