Intraneuronal Neurofibrillary Tangles Isolated from Alzheimer’ Disease Affected Brains Visualized by Vertical Platinum-Carbon Replication for TEM

Abstract Neurofibrillary tangles (NFT) occur with high frequency in brains of patients with Alzheimer' disease (AD). The frequency of NFT directly correlates with the degree of dementia. Extra cellular plaque core amyloid also occurs in high frequently in AD brains when few intraneuronal NFT are present, these individuals are not demented. The microtubule associated protein (MAP) tau is recognized as the principal constituent in paired helical filaments (PHF) and NFT. NFT contain PHF, amorphous structures containing tau, and a triple-stranded left-hand helical ˜2.1 nm filament similar to tau polymer which has been identified in isolated tangles. Tau is located in nerve cell axons and associates with and stabilizes the microtubules required for axonal transport. Sequestration of tau into tangles and its removal from microtubules not only compromises axonal transport but cripples synaptic communication between nerve cells. NFT were isolated in the absence of detergent so these gel-like structures (Fig. 1) could be studied at the molecular level.