[37] Isolation of paired helical filaments and amyloid fibers from human brain

1986 ◽  
pp. 388-404 ◽  
Author(s):  
Dennis J. Selkoe ◽  
Carmela R. Abraham
Keyword(s):  
Human Brain ◽  
Paired Helical Filaments ◽  
Amyloid Fibers

scholarly journals Epitope mapping of monoclonal antibodies to the paired helical filaments of Alzheimer's disease: identification of phosphorylation sites in tau protein

1994 ◽  
Vol 301 (3) ◽  
pp. 871-877 ◽  
Author(s):  
M Goedert ◽  
R Jakes ◽  
R A Crowther ◽  
P Cohen ◽  
E Vanmechelen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Epitope Mapping ◽  
Paired Helical Filaments ◽  
Phosphorylation Sites ◽  
Paired Helical Filament ◽  
Developmentally Regulated ◽  
Specific Amino Acid ◽  
Tau Isoforms

Tau is a neuronal phosphoprotein the expression of which is developmentally regulated. A single tau isoform is expressed in fetal human brain but six isoforms are expressed in adult human brain, with the fetal isoform corresponding to the shortest adult isoform. Phosphorylation is also developmentally regulated, as fetal tau is phosphorylated at more sites than adult tau. In Alzheimer's disease, the six adult tau isoforms become hyperphosphorylated and form the paired helical filament (PHF), the major fibrous component of the neurofibrillary lesions. One way to identify phosphorylated sites in tau is to use antibodies that recognize phosphorylated residues within a specific amino acid sequence. We here characterize the two novel phosphorylation-dependent anti-tau antibodies AT270 and AT180 and identify their epitopes as containing phosphorylated Thr-181 and Thr-231 respectively. With these antibodies we show that these two threonine residues are partially phosphorylated in fetal and adult tau and almost fully phosphorylated in PHF tau. This result contrasts with previous studies of Ser-202 and Ser-396 which are partially phosphorylated in fetal tau, unphosphorylated in adult tau but almost fully phosphorylated in PHF tau.

Language processing is not a race against time

2016 ◽  
Vol 39 ◽  
Author(s):  
Giosuè Baggio ◽  
Carmelo M. Vicario
Keyword(s):  
Information Processing ◽  
Human Brain ◽  
Language Processing ◽  
Cognitive Functions ◽  
Memory Systems ◽  
Language System ◽  
Moderating Factors

AbstractWe agree with Christiansen & Chater (C&C) that language processing and acquisition are tightly constrained by the limits of sensory and memory systems. However, the human brain supports a range of cognitive functions that mitigate the effects of information processing bottlenecks. The language system is partly organised around these moderating factors, not just around restrictions on storage and computation.

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.

Alzheimer's Paired Helical Filaments Contain Insoluble Cytoskeletal Elements

1985 ◽  
Vol 43 ◽  
pp. 748-751
Author(s):  
P. Gambetti ◽  
G. Perry ◽  
L. Autillo-Gambetti
Keyword(s):  
Paired Helical Filaments ◽  
Microscope Level ◽  
Antigenic Determinants ◽  
Light Microscope Level ◽  
Neuronal Cytoskeleton ◽  
Ionic Detergent ◽  
Associated Proteins ◽  
Pathologic Lesions ◽  
10 Nm Filaments ◽  
Cytoskeletal Elements

Neurofibrillary tangles (NFT) are one of the major pathologic lesions of Alzheimer's disease. These neuronal inclusions are predominantly composed of paired helical filaments (PHF), which consist of two 10 nm filaments winding around each other with an approximately 80 nm periodicity. Besides PHF, NFT comprise also 15 nm filaments, 10 nm filaments which are probably neurofilaments, microtubules and granular material. At variance with the neuronal cytoskeleton, PHF are insoluble in ionic detergent.Studies at the light microscope level have shown that NFT have unique antigenic determinants as well as determinants in common with elements of the normal neuronal cytoskeleton such as neurofilaments and microtubule-associated proteins. The present study uses immunocytochemistry and cytochemistry at the electron microscope level to assess which NFT component contains these determinants and whether these antigenic determinants are soluble in an ionic detergent.

Neurofilaments and Paired Helical Filaments

1985 ◽  
Vol 43 ◽  
pp. 740-743
Author(s):  
J. Metuzals
Keyword(s):  
Animal Model ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Giant Axon ◽  
Paired Helical Filaments ◽  
Squid Giant Axon ◽  
In Vitro Experiments ◽  
Thin Sections ◽  
Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

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.

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