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.

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.

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 protein and its role in Alzheimer’s disease physiopathology: a literature review

2021 ◽  
Author(s):  
Larissa Rosa Stork ◽  
Lucca Stephani Ribeiro ◽  
Izabella Savergnini Deprá ◽  
Luísa D’Ávila Camargo ◽  
Maria Angélica Santos Novaes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Paired Helical Filaments ◽  
Tau Proteins ◽  
Molecular Aspects ◽  
Cellular Cytoskeleton

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a double proteinopathy: deposition of amyloid-β into plaques and hyperphosphorylation of Tau protein. Objectives: To understand the genetic and molecular aspects of Tau protein and its relationship with Alzheimer’s disease. Methods: We conducted a systematic literature search using Pubmed/ MEDLINE and ClinicalKey databases, applying the descriptors: “Alzheimer Disease” AND “Tau proteins’’ AND Tauopathies, during July and August of 2020. The inclusion criteria were English and Portuguese articles published between 2015 and 2020, with human limited study and free full text, excluding images, books, clinical tests, and narrative reviews. After analyzing titles and abstracts, we selected 12 articles and included 7 additional studies. Results: Mapt, the encoder gene of Tau, is located in the 17q21.3 locus and presents 16 exons that, when transcripted, originates 12 copies of mRNA by alternative splicing and 6 Tau’s isoforms. Tau is a microtubule-associated protein (MAP) responsible for cellular cytoskeleton stabilization and maintenance, promoting neuronal axonal transport. A kinase-phosphatase imbalance turns Tau hyperphosphorylated, disassociating it from tubulin and grouping it into insoluble paired helical filaments, which originates neurofibrillary tangles. The tauopathy’s progress causes neurotransmitter destabilization and neuronal death, inducing AD symptomatic manifestations. Conclusions: Due to the gradual worsening of the disease to more debilitating stages, studies focused on deepening the knowledge of genetic and molecular aspects of Tau protein are viable and promising alternatives to improve the quality of patient’s lives.

scholarly journals Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies

2021 ◽  
Vol 22 (17) ◽  
pp. 9207 ◽  
Author(s):  
Jakub Sinsky ◽  
Karoline Pichlerova ◽  
Jozef Hanes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Critical Role ◽  
Neuronal Loss ◽  
Paired Helical Filaments ◽  
Normal Function ◽  
Tau Proteins ◽  
Proper Function ◽  
Interaction Partners

Tau protein plays a critical role in the assembly, stabilization, and modulation of microtubules, which are important for the normal function of neurons and the brain. In diseased conditions, several pathological modifications of tau protein manifest. These changes lead to tau protein aggregation and the formation of paired helical filaments (PHF) and neurofibrillary tangles (NFT), which are common hallmarks of Alzheimer’s disease and other tauopathies. The accumulation of PHFs and NFTs results in impairment of physiological functions, apoptosis, and neuronal loss, which is reflected as cognitive impairment, and in the late stages of the disease, leads to death. The causes of this pathological transformation of tau protein haven’t been fully understood yet. In both physiological and pathological conditions, tau interacts with several proteins which maintain their proper function or can participate in their pathological modifications. Interaction partners of tau protein and associated molecular pathways can either initiate and drive the tau pathology or can act neuroprotective, by reducing pathological tau proteins or inflammation. In this review, we focus on the tau as a multifunctional protein and its known interacting partners active in regulations of different processes and the roles of these proteins in Alzheimer’s disease and tauopathies.

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.

Neurofibrillary tangles and tau phosphorylation

2001 ◽  
Vol 67 ◽  
pp. 81-88 ◽  
Author(s):  
Jean-Pierre Brion ◽  
Brian H. Anderton ◽  
Michéle Authelet ◽  
Rejith Dayanandan ◽  
Karelle Leroy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Neurofibrillary Tangles ◽  
Glycogen Synthase ◽  
Tau Phosphorylation ◽  
Precursor Protein ◽  
Tau Proteins ◽  
Chromosome 17 ◽  
Transfected Cells

Neurofibrillary tangles (NFTs) are a characteristic neuropathological lesion of Alzheimer's disease (AD). They are composed of a highly-phosphorylated form of the microtubule-associated protein tau. We are investigating the relationship between NFTs and microtubule stability and how tau phosphorylation and function is affected in transgenic models and by co-expression with ϐ-amyloid precursor protein and presenilins. In most NFT-bearing neurons, we observed a strong reduction in acetylated α-tubulin immunoreactivity (a marker of stable microtubules) and a reduction of the in situ hybridization signal for tubulin mRNA. In transfected cells, mutated tau forms (corresponding to tau mutations identified in familial forms of frontotemporal dementias linked to chromosome 17) were less efficient in their ability to sustain microtubule growth. These observations are consistent with the hypothesis that destabilization of the microtubule network is an important mechanism of cell dysfunction in Alzheimer's disease. The glycogen synthase kinase-3 ϐ (GSK-3ϐ) generates many phosphorylated sites on tau. We performed a neuroanatomical study of GSK-3ϐ distribution showing that developmental evolution of GSK-3ϐ compartmentalization in neurons paralleled that of phosphorylated tau. Studies on transfected cells and on cultured neurons showed that GSK-3 ϐ activity controls tau phosphorylation and tau functional interaction with microtubules. Tau phosphorylation was not affected in neurons overexpressing ϐ-amyloid precursor protein. Transgenic mice expressing a human tau isoform and double transgenic animals for tau and mutated presenilin 1 have been generated; a somatodendritic accumulation of phosphorylated transgenic tau proteins, as observed in the pretangle stage in AD, has been observed but NFTs were not found, suggesting that additional factors might be necessary to induce their formation.

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