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

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.

Statistical geometric analysis of packing of paired helical filaments in neurofibrillary tangles of Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 840-841
Author(s):  
D. F. Clapin ◽  
V.J.A. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Geometric Analysis ◽  
Paired Helical Filaments ◽  
Thin Sections ◽  
Present Evidence ◽  
Longitudinal Orientation ◽  
Low Probability

The tangles of abnormal fibers known as paired helical filaments (PHF), which occur in neurons of persons suffering from Alzheimer's disease, possess limited regions of quasi-crystalline ordering interspersed with regions of randomly oriented fibers. Analysis of the quasi-crystalline zones of tangles, as visualized in longitudinal orientation in thin sections, indicated that a paracrystalline order may characterize the packing of PHF in tangles. Para-crystals may be defined as structures in which each pair of molecules is associated with uniquely spaced positions with a low probability that the molecules occupy these positions. In a paracrystal of the first kind, the probability of the molecules occupying these positions is independent of the distance from an arbitrary origin. In a paracrystal of the second type, positional indeterminancy increases with increasing distance. Myelin is a paracrystal of the second kind. The purpose of this paper is to present evidence concerning the paracrystalline nature of PHF in Alzheimer tangles based on analyses of variance of PHF interfilament spacing.

The fine structure of dementing illness: Alzheimer's disease and AIDS

1987 ◽  
Vol 45 ◽  
pp. 612-615
Author(s):  
S. S. Mirra ◽  
M. L. Miles ◽  
C. del Rio ◽  
M. H. Ellisman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fine Structure ◽  
Neurofibrillary Tangles ◽  
Brain Biopsy ◽  
Paired Helical Filaments ◽  
Apical Dendrite ◽  
Voltage Electron ◽  
Electron Microscopes ◽  
Axonal Protein

Electron microscopy has made important contributions to our understanding of dementing illnesses. The fine structure of neurofibrillary tangles and neuritic plaques, the pathologic hallmarks of Alzheimer's disease, was first described in the early 1960's. Yet, the nature of paired helical filaments, constituents of neurofibrillary tangles and some plaque neurites, has remained an enigma. Recent studies indicate that a major component of paired helical filaments is an atypically phosphorylated form of the microtubule-associated protein, tau. The finding of tau, normally an axonal protein, within neurofibrillary tangles of cell body and apical dendrite suggests that abnormalities in segregation and modification of this microtubule-associated protein may be defective in Alzheimer's disease.The availability of brain biopsy specimens from five cases of neuropathologically confirmed Alzheimer's disease provided the opportunity for study of well-preserved tissue. Thin and thick sections (0.25-0.75 um) viewed on conventional and high voltage electron microscopes revealed sidearms or extensions projecting at irregular intervals along the paired helical filaments.

scholarly journals Tau in Alzheimer neurofibrillary tangles. N- and C-terminal regions are differentially associated with paired helical filaments and the location of a putative abnormal phosphorylation site

1991 ◽  
Vol 273 (1) ◽  
pp. 127-133 ◽  
Author(s):  
J P Brion ◽  
D P Hanger ◽  
M T Bruce ◽  
A M Couck ◽  
J Flament-Durand ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Phosphorylation Site ◽  
Paired Helical Filaments ◽  
Tau Proteins ◽  
Ultrastructural Appearance ◽  
Pronase Treatment ◽  
Terminal Domains

To investigate the extent to which whole tau proteins, structurally abnormal tau and fragments of tau are incorporated into neurofibrillary tangles in Alzheimer's disease, an immunocytochemical mapping study using a panel of antibodies to several synthetic human tau peptides has been performed. Neurofibrillary tangles were immunolabelled in situ, and paired helical filaments (PHF), the principal structural component of tangles, were immunolabelled after isolation and Pronase treatment. N-Terminal and C-terminal domains of tau were found to be present in tangles in situ. SDS-treated PHF were found to contain most of the C-terminal half of tau and were also labelled by antibodies to ubiquitin. Only some of these PHF were labelled by antisera to tau sequences towards the N-terminus, and this enabled the identification of a region of tau in which proteolytic cleavage may occur. The ultrastructural appearance of the immunolabelling suggested that both the N- and C-terminal domains of tau extend outwards from the axis of PHF. After Pronase treatment. PHF were strongly labelled only by an antiserum to PHF and by the antiserum to the most C-terminal tau synthetic peptide. The latter antiserum also strongly labelled extracellular tangles in situ, whereas these extracellular tangles were poorly labelled by the antisera to the other synthetic peptides. One anti-(tau peptide) serum labelled a population of neurofibrillary tangles in situ only after alkaline phosphatase pretreatment of tissue sections. Our results show that, although peptides along the length of the tau molecule are associated with neurofibrillary tangles in situ, only the C-terminal one-third of the molecule is tightly associated with PHF, since this region of tau is resistant to SDS treatment of PHF. We also report the existence in PHF in situ of a masked tau epitope which is partially unmasked by dephosphorylation. These results are indicative of post-translational changes in tangle-associated tau in degenerating neurons in Alzheimer's disease.

scholarly journals The twisted tauopathies: surface interactions of helically patterned filaments seen in alzheimer's disease and elsewhere

Soft Matter ◽  
2016 ◽  
Vol 12 (3) ◽  
pp. 779-789 ◽  
Author(s):  
Nash D. Rochman ◽  
Sean X. Sun
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cross Section ◽  
Neurofibrillary Tangles ◽  
Amyloid Fibrils ◽  
Mechanistic Explanation ◽  
Surface Interactions

Here we provide a mechanistic explanation for the conversion of CF-PT amyloid fibrils (b and a cross-section) to PHF amyloid fibrils (c and d) thought to be important in the aggregation of pathological neurofibrillary tangles characteristic of Alzheimer's disease.

Formation of paired helical filaments in Alzheimer's disease

1984 ◽  
Vol 42 ◽  
pp. 302-303
Author(s):  
J. Metuzals ◽  
D. F. Clapin ◽  
V. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontal Lobe ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Normal Brain ◽  
Protein Assemblies ◽  
Electron Microscopic ◽  
Helical Symmetry ◽  
Structural Levels

Information on the conformation of paired helical filaments (PHF) and the neurofilamentous (NF) network is essential for an understanding of the mechanisms involved in the formation of the primary lesions of Alzheimer's disease (AD): tangles and plaques. The structural and chemical relationships between the NF and the PHF have to be clarified in order to discover the etiological factors of this disease. We are investigating by stereo electron microscopic and biochemical techniques frontal lobe biopsies from patients with AD and squid giant axon preparations. The helical nature of the lesion in AD is related to pathological alterations of basic properties of the nervous system due to the helical symmetry that exists at all hierarchic structural levels in the normal brain. Because of this helical symmetry of NF protein assemblies and PHF, the employment of structure reconstruction techniques to determine the conformation, particularly the handedness of these structures, is most promising. Figs. 1-3 are frontal lobe biopsies.

Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 842-843
Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Paired Helical Filaments ◽  
Ethanol Intoxication ◽  
Drg Neurons ◽  
Critical Difference ◽  
Suitable Animal Model ◽  
The Central Nervous System ◽  
Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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