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

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.

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The microtubule associated protein (MAP) tau forms a new class of triple-stranded left-hand helical fibrous protein polymer

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123106 ◽

1992 ◽

Vol 50 (1) ◽

pp. 540-541

Author(s):

G. C. Ruben ◽

K. Iqbal ◽

I. Grundke-Iqbal ◽

H. Wisniewski ◽

T. L. Ciardelli ◽

...

Keyword(s):

Axial Ratio ◽

Normal Structure ◽

Paired Helical Filaments ◽

Left Hand ◽

New Class ◽

Protein Polymer ◽

Fibrous Protein ◽

Protein Map ◽

Neurotransmitter Transport ◽

Alzheimer Neurofibrillary Tangles

In neurons, the microtubule associated protein, tau, is found in the axons. Tau stabilizes the microtubules required for neurotransmitter transport to the axonal terminal. Since tau has been found in both Alzheimer neurofibrillary tangles (NFT) and in paired helical filaments (PHF), the study of tau's normal structure had to preceed TEM studies of NFT and PHF. The structure of tau was first studied by ultracentrifugation. This work suggested that it was a rod shaped molecule with an axial ratio of 20:1. More recently, paraciystals of phosphorylated and nonphosphoiylated tau have been reported. Phosphorylated tau was 90-95 nm in length and 3-6 nm in diameter where as nonphosphorylated tau was 69-75 nm in length. A shorter length of 30 nm was reported for undamaged tau indicating that it is an extremely flexible molecule. Tau was also studied in relation to microtubules, and its length was found to be 56.1±14.1 nm.

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Liquid crystalline ordering of paired helical filaments in neurofibrillary tangles of Alzheimer's disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100143365 ◽

1986 ◽

Vol 44 ◽

pp. 348-349

Author(s):

D.F. Clapin ◽

V.J.A. Montpetit

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurofibrillary Tangles ◽

Liquid Crystalline ◽

Amyloid Fibrils ◽

Geometric Analysis ◽

Paired Helical Filaments ◽

Microscopic Level ◽

Light Microscopic Level ◽

Regular Spacing

Alzheimer's disease is characterized by the accumulation of abnormal filamentous proteins. The most important of these are amyloid fibrils and paired helical filaments (PHF). PHF are located intraneuronally forming bundles called neurofibrillary tangles. The designation of these structures as "tangles" is appropriate at the light microscopic level. However, localized domains within individual tangles appear to demonstrate a regular spacing which may indicate a liquid crystalline phase. The purpose of this paper is to present a statistical geometric analysis of PHF packing.

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Structural and Chemical Studies of Pathological Fibers in Human Neurofibrillary Degeneration

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012031x ◽

1985 ◽

Vol 43 ◽

pp. 726-729

Author(s):

K.S. Kosik ◽

L.K. Duffy ◽

S. Bakalis ◽

C. Abraham ◽

D.J. Selkoe

Keyword(s):

Monoclonal Antibodies ◽

Alzheimer Disease ◽

Human Brain ◽

Neurofibrillary Tangles ◽

Morphological Analysis ◽

High Specificity ◽

Cytoskeletal Proteins ◽

Neuritic Plaque ◽

Protein Chemistry ◽

Chemical Studies

The major structural lesions of the human brain during aging and in Alzheimer disease (AD) are the neurofibrillary tangles (NFT) and the senile (neuritic) plaque. Although these fibrous alterations have been recognized by light microscopists for almost a century, detailed biochemical and morphological analysis of the lesions has been undertaken only recently. Because the intraneuronal deposits in the NFT and the plaque neurites and the extraneuronal amyloid cores of the plaques have a filamentous ultrastructure, the neuronal cytoskeleton has played a prominent role in most pathogenetic hypotheses.The approach of our laboratory toward elucidating the origin of plaques and tangles in AD has been two-fold: the use of analytical protein chemistry to purify and then characterize the pathological fibers comprising the tangles and plaques, and the use of certain monoclonal antibodies to neuronal cytoskeletal proteins that, despite high specificity, cross-react with NFT and thus implicate epitopes of these proteins as constituents of the tangles.

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