Structure of β-amyloid fibrils and its relevance to their neurotoxicity: Implications for the pathogenesis of Alzheimer’s disease

2005 ◽  
Vol 99 (5) ◽  
pp. 437-447 ◽  
Author(s):  
Kazuhiro Irie ◽  
Kazuma Murakami ◽  
Yuichi Masuda ◽  
Akira Morimoto ◽  
Hajime Ohigashi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Β Amyloid

scholarly journals Molecular Structure of β-Amyloid Fibrils in Alzheimer’s Disease Brain Tissue

Cell ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 1257-1268 ◽  
Author(s):  
Jun-Xia Lu ◽  
Wei Qiang ◽  
Wai-Ming Yau ◽  
Charles D. Schwieters ◽  
Stephen C. Meredith ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Amyloid Fibrils ◽  
Β Amyloid

β-Amyloid Peptide and Amyloid Precursor Proteins in Olfactory Mucosa of Patients with Alzheimer's Disease, Parkinson's Disease, and down Syndrome

1995 ◽  
Vol 104 (8) ◽  
pp. 655-661 ◽  
Author(s):  
Peter B. Crino ◽  
Barry Greenberg ◽  
John A. Martin ◽  
Virginia M.-Y. Lee ◽  
William D. Hill ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Down Syndrome ◽  
Amyloid Fibrils ◽  
Olfactory Mucosa ◽  
Amyloid Peptide ◽  
Β Amyloid

Dystrophic neurites are present in olfactory epithelium (OE) of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and Down syndrome (DS) and occasionally in normal individuals. Cultured olfactory neuroblasts from AD patients generate carboxy terminal amyloid precursor protein (APP) fragments that contain β-amyloid (Aβ), but it is not known if deposits of Aβ and/or APP fragments occur in the OE of individuals with or without AD, PD, or DS. To determine if Aβ accumulates in the OE in situ, we probed postmortem samples of olfactory mucosa from patients with AD, PD and AD (PD/AD), and DS and AD (DS/AD), as well as from controls, using polyclonal and monoclonal antibodies to Aβ and flanking sequences in APPs. Samples of OE also were examined by thioflavin-S and electron microscopy. Labeling of Aβ was observed in 10 of 12 AD cases, 2 of 3 PD/AD cases, 3 of 4 DS/AD cases, 3 of 10 adult controls, and 4 of 6 fetal cases. The Aβ staining was seen in the basal third of the OE, in axons projecting through the lamina propria, and in metaplastic respiratory epithelium within the OE. Antibodies to other APP domains stained the OE of patients and controls. Thioflavin-S staining was present in the basal third of the OE of 8 of 9 AD patients and several PD/AD and DS/AD patients, but only in rare cells of 3 controls. Electron microscopy did not reveal amyloid fibrils in the OE. These data suggest that deposition of Aβ occurs in a variety of circumstances and is not restricted to patients with AD, PD, or DS.

Imaging β-amyloid fibrils in Alzheimer's disease: a critical analysis through simulation of amyloid fibril polymerization

2005 ◽  
Vol 32 (4) ◽  
pp. 337-351 ◽  
Author(s):  
Kooresh Shoghi-Jadid ◽  
Jorge R. Barrio ◽  
Vladimir Kepe ◽  
Hsiao-Ming Wu ◽  
Gary W. Small ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Critical Analysis ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Β Amyloid

Modification of membrane lipids protects neurons against insulin resistance in models of Alzheimer’s disease

e-Neuroforum ◽  
2017 ◽  
Vol 23 (4) ◽  
Author(s):  
Viola Nordström ◽  
Silke Herzer
Keyword(s):  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Membrane Lipids ◽  
Insulin Receptors ◽  
Amyloid Oligomers ◽  
The Central Nervous System ◽  
Β Amyloid ◽  
Neuronal Insulin Resistance

AbstractAlzheimer’s disease is a degenerative disease of the central nervous system, which leads to severe deficits in memory and orientation by a progressive loss of neurons and synapses. Soluble β-amyloid oligomers are highly neurotoxic precursors of β-amyloid fibrils that accumulate in Alzheimer’s disease. Binding of β-amyloid oligomers to synaptic insulin receptors leads to neuronal insulin resistance, which significantly contributes to cognitive impairments.Insulin receptors are located in the cell membrane, which consists of a lipid bilayer and contains high amounts of glycosylated lipids, the so-called gangliosides. Gangliosides regulate insulin receptor activity via dynamic molecular interactions and facilitate the β-amyloid oligomer-induced insulin resistance. Thus, inhibiting ganglioside biosynthesis can protect neurons from the detrimental effects of β-amyloid oligomers.

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.

Аnticholinesterase and antioxidant activity of new binary conjugates of (с)-carbolines

2019 ◽  
Vol 484 (1) ◽  
pp. 104-108
Author(s):  
G. F. Makhaeva ◽  
E. F. Shevtsova ◽  
N. P. Boltneva ◽  
N. V. Kovaleva ◽  
E. V. Rudakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Anticholinesterase Activity ◽  
Amyloid Aggregation ◽  
Varying Length ◽  
Β Amyloid ◽  
New Compounds

This study presents the synthesis of binary tetrohydro-γ-carbolines with ditriazol spacers of varying length, which exhibit anticholinesterase and antioxidant activity, as compared to the original Dimebon prototype. Anticholinesterase activity suggests the potential ability of the new compounds to block β-amyloid aggregation induced by anticholinesterase, making them promising candidates for further research preparations for the treatment of Alzheimer's disease. Particular attention should be paid to the conjugate with an intertriazol hexamethylene spacer, which can be regarded as the leading compound in this series.

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