Types Of Tangles Research Articles

Immunohistochemical staging of neurofibrillary degeneration in Alzheimer's disease.

Antibodies to different phosphorylated and non-phosphorylated tau epitopes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughout the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed extracellular tangles (Type 3) were characterized by the presence of epitopes associated with the microtubule binding region and the COOH-terminus. These three types of tangles, found in situ in hippocampus, could be created experimentally by proteolytic treatment of brain sections. These findings suggest that three stages of neurofibrillary degeneration can be understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phosphorylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.

Paired helical filaments (PHF) in Alzheimer disease are phosphorylated at multiple sites : ∗L.R. Murthy and K. Iqbal. Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA

Antisera were raised in rabbits to purified bovine tau and to isolated Alzheimer paired helical filaments (PHF) washed with sodium dodecyl sulfate (SDS). Both anti-tau and anti-PHF sera labeled at electron microscopic level PHF which had been isolated either by extraction with SDS or treatment with crude collagenase. On immunoblots all anti-tau and anti-PHF sera labeled bovine brain tau as well as the major 45- to 62-kDa PHF polypeptides which had been previously shown to co-migrate on SDS gels with normal human tau (J. Biol. Chem., 261 (1986) 6084–6089). All antisera labeled Alzheimer neurofibrillary tangles on tissue sections and the PHF polypeptides on immunoblots. Pretreatment with alkaline phosphatase had no effect on the immunostaining. The antisera did not react with ubiquitin, neurofilament triplet polypeptides and with the exception of one antiserum with tubulin and high-molecular weight microtubule-associated proteins. Absorption of tau antisera with tau and PHF and of PHF antisera with PHF resulted in complete removal of the tangles-staining antibodies. In case of the anti-PHF sera when absorbed with tau, only the staining of a certain tangles population, the dense type, was eliminated and that too at more than 20 times the amount needed for the anti-tau sera; the staining of the loosely packed type of tangles, presumably the final stage, gradually decreased but was not completely abolished. On immunoblots the tau-like major PHF bands remained labeled by the tau-absorbed anti-PHF sera. These studies indicate that tau in PHF is present in different states of modification and that these alterations in tau are in addition to the abnormal phosphorylation shown previously (Proc. Natl. Acad. Sci. U.S.A., 83 (1986) 4913–4917).

Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments

Antisera were raised in rabbits to purified bovine tau and to isolated Alzheimer paired helical filaments (PHF) washed with sodium dodecyl sulfate (SDS). Both anti-tau and anti-PHF sera labeled at electron microscopic level PHF which had been isolated either by extraction with SDS or treatment with crude collagenase. On immunoblots all anti-tau and anti-PHF sera labeled bovine brain tau as well as the major 45- to 62-kDa PHF polypeptides which had been previously shown to co-migrate on SDS gels with normal human tau ( J. Biol. Chem., 261 (1986) 6084–6089). All antisera labeled Alzheimer neurofibrillary tangles on tissue sections and the PHF polypeptides on immunoblots. Pretreatment with alkaline phosphatase had no effect on the immunostaining. The antisera did not react with ubiquitin, neurofilament triplet polypeptides and with the exception of one antiserum with tubulin and high-molecular weight microtubule-associated proteins. Absorption of tau antisera with tau and PHF and of PHF antisera with PHF resulted in complete removal of the tangles-staining antibodies. In case of the anti-PHF sera when absorbed with tau, only the staining of a certain tangles population, the dense type, was eliminated and that too at more than 20 times the amount needed for the anti-tau sera; the staining of the loosely packed type of tangles, presumably the final stage, gradually decreased but was not completely abolished. On immunoblots the tau-like major PHF bands remained labeled by the tau-absorbed anti-PHF sera. These studies indicate that tau in PHF is present in different states of modification and that these alterations in tau are in addition to the abnormal phosphorylation shown previously ( Proc. Natl. Acad. Sci. U.S.A., 83 (1986) 4913–4917).

Strain hardening and structural changes in molybdenum in tension with the application of ultrasonic vibrations

1. In the tension of molybdenum with the application of ultrasonic vibrations the general rules of strain hardening according to a multistage plan are observed, but under the influence of the ultrasonic vibrations the stage of parabolic hardening with a tangle type dislocation structure is significantly broadened within the studied range of amplitudes and a later transition to the stage of formation of the dislocation cell structure is noted. 2. The relationship of the parameters of strain hardening and of the dimensions of the cell structure to the amplitude of the ultrasonic vibrations have a complex inconsistent structure caused by the simultaneous action of competing mechanisms of softening (the ultrasonic vibrations reduce the resistance to dislocation movement) and hardening (ultrasonic vibrations of larger amplitude cause the generation of new additional dislocations).

Senile dementia of Alzheimer type: astroglial reaction to extracellular neurofibrillary tangles in the hippocampus. An immunocytochemical and electron-microscopic study.

Two types of Alzheimer neurofibrillary tangles may be found in the hippocampus in senile dementia of the Alzheimer type. Besides classical flame-shaped intraneuronal tangles, there are less compact tangles representing extracellular remnants of destroyed neurons with neurofibrillary change. Strong immunoreactivity for glial fibrillary acidic protein (GFA) was found in the second type of tangles, which was due to penetration of fine processes of fibrous astrocytes into bundles of paired helical filaments (PHF). PHF appear to be a strong stimulus for astrocytic reaction when they are not segregated from the neuropil by the neuronal cell membrane.

Neurofibrillary changes in the cerebral cortex of a patient with subacute sclerosing panencephalitis (SSPE).

Biopsy fragments from the frontal cortex of one patient with SSPE were studied with ultrastructural methods. Special attention was given to the presence of neurofibrillary tangles observed in all cortical layers. These tangles were composed either of filaments with a diameter of 10 -- 12 nm or of paired helical filaments 22 -- 24 nm at their widest and periodically reduced to 10 nm about every 80 nm. These tangles were observed in all cortical layers, while those formed by single filaments were only visualized in layer 3. The simultaneous appearance of both types of tangles in the same patient suggests that they may be chemically related, which is in keeping with recent chemical data concerning the nature of the neurofilament protein subunit.

Electron microscopic study of neurofibrillary tangles in Steele-Richardson-Olszewski syndrome.

The neurofibrillary tangles found in the neurons of a case of Steele-Richardson-Olszewski syndrome were studied by electron microscopy. Both the flame-shaped and globose type of tangles were present. The neurofibrillary tangles were composed of bundles of straight tubules measuring approximately 150 A in diameter. This ultrastructural appearance of the tangles in Steele-Richardson-Olszewski syndrome is different from the appearance of tangles found in other neurological disorders and is probably indicative of intraneuronal accumulation of a new type of fibrous protein.

Dislocation structures in deformed and recovered tantalum

Dislocation structures in deformed tantalum were examined using transmission electron microscopy. It was found that the deformation structures formed in tantalum strained at temperatures between 25° and 1000°C are comparable to those found in iron on the basis of homologous deformation temperatures. Several observations pertaining to the distribution of tangles at low strains, the types of tangles formed, the mechanisms of tangle formation, and the formation of deformation cell structure from tangles are also reported.