Masters, CL, Multhaup, G, Simms, G, Pottgiesser, J, Martins, RN and Beyreuther, K. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4: 2757-2763

The EMBO Journal (Impact Factor: 10.43). 12/1985; 4(11):2757-63.
Source: PubMed


The protein component of Alzheimer's disease amyloid [neurofibrillary tangles (NFT), amyloid plaque core and congophilic angiopathy] is an aggregated polypeptide with a subunit mass of 4 kd (the A4 monomer). Based on the degree of N-terminal heterogeneity, the amyloid is first deposited in the neuron, and later in the extracellular space. Using antisera raised against synthetic peptides, we show that the N terminus of A4 (residues 1-11) contains an epitope for neurofibrillary tangles, and the inner region of the molecule (residues 11-23) contains an epitope for plaque cores and vascular amyloid. The non-protein component of the amyloid (aluminum silicate) may form the basis for the deposition or amplification (possible self-replication) of the aggregated amyloid protein. The amyloid of Alzheimer's disease is similar in subunit size, composition but not sequence to the scrapie-associated fibril and its constituent polypeptides. The sequence and composition of NFT are not homologous to those of any of the known components of normal neurofilaments.

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Available from: Colin L Masters, Sep 30, 2015
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    • "In 1984, Glenner and Wong isolated a novel peptide derived from AD-linked cerebrovascular pathology (Glenner and Wong, 1984). One year later, Masters and co-workers found that the same peptide, termed amyloid-β peptide (Aβ), is the principal component of amyloid plaque cores isolated from AD brains (Masters et al., 1985). Aβ is a 4 kDa peptide (with 40-and 42-amino acid residue peptides as the predominant species) derived from proteolytic cleavage of a precursor protein termed amyloid precursor protein (APP; Kang et al., 1987; De Felice et al., 2004; Gralle and Ferreira, 2007). "
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    ABSTRACT: Alzheimer’s disease (AD) is the most common form of dementia in the elderly, and affects millions of people worldwide. As the number of AD cases continues to increase in both developed and developing countries, finding therapies that effectively halt or reverse disease progression constitutes a major research and public health challenge. Since the identification of the amyloid-b peptide (Ab) as the major component of the amyloid plaques that are characteristically found in AD brains, a major effort has aimed to determine whether and how Ab leads to memory loss and cognitive impairment. A large body of evidence accumulated in the past 15 years supports a pivotal role of soluble Ab oligomers (AbOs) in synapse failure and neuronal dysfunction in AD. Nonetheless, a number of basic questions, including the exact molecular composition of the synaptotoxic oligomers, the identity of the receptor(s) to which they bind, and the signaling pathways that ultimately lead to synapse failure, remain to be definitively answered. Here, we discuss recent advances that have illuminated our understanding of the chemical nature of the toxic species and the deleterious impact they have on synapses, and have culminated in the proposal of an Ab oligomer hypothesis for Alzheimer’s pathogenesis. We also highlight outstanding questions and challenges in AD research that should be addressed to allow translation of research findings into effective AD therapies.
    Frontiers in Cellular Neuroscience 05/2015; 9. DOI:10.3389/fncel.2015.00191 · 4.29 Impact Factor
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    • "Mice overexpressing mutated human amyloid precursor protein (APP) from which amyloid-b is derived, exhibit synaptic deficits even in the absence of marked plaque formation, implicating soluble amyloid-b oligomers in Alzheimer pathogenesis (Mucke et al., 2000; Tomiyama et al., 2010). Amyloid-b is generated in neurons throughout the brain (Masters et al., 1985; Goedert, 1987), and can also be endocytosed (Knauer et al., 1992). Gouras et al. (2000) observed region-specific accumulation of amyloid-b in pyramidal neurons of the hippocampus, layer II of entorhinal cortex, and, notably, in BFCNs. "
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    ABSTRACT: The mechanisms that contribute to selective vulnerability of the magnocellular basal forebrain cholinergic neurons in neurodegenerative diseases, such as Alzheimer's disease, are not fully understood. Because age is the primary risk factor for Alzheimer's disease, mechanisms of interest must include age-related alterations in protein expression, cell type-specific markers and pathology. The present study explored the extent and characteristics of intraneuronal amyloid-β accumulation, particularly of the fibrillogenic 42-amino acid isoform, within basal forebrain cholinergic neurons in normal young, normal aged and Alzheimer's disease brains as a potential contributor to the selective vulnerability of these neurons using immunohistochemistry and western blot analysis. Amyloid-β1-42 immunoreactivity was observed in the entire cholinergic neuronal population regardless of age or Alzheimer's disease diagnosis. The magnitude of this accumulation as revealed by optical density measures was significantly greater than that in cortical pyramidal neurons, and magnocellular neurons in the globus pallidus did not demonstrate a similar extent of amyloid immunoreactivity. Immunoblot analysis with a panel of amyloid-β antibodies confirmed accumulation of high concentration of amyloid-β in basal forebrain early in adult life. There was no age- or Alzheimer-related alteration in total amyloid-β content within this region. In contrast, an increase in the large molecular weight soluble oligomer species was observed with a highly oligomer-specific antibody in aged and Alzheimer brains when compared with the young. Similarly, intermediate molecular weight oligomeric species displayed an increase in aged and Alzheimer brains when compared with the young using two amyloid-β42 antibodies. Compared to cortical homogenates, small molecular weight oligomeric species were lower and intermediate species were enriched in basal forebrain in ageing and Alzheimer's disease. Regional and age-related differences in accumulation were not the result of alterations in expression of the amyloid precursor protein, as confirmed by both immunostaining and western blot. Our results demonstrate that intraneuronal amyloid-β accumulation is a relatively selective trait of basal forebrain cholinergic neurons early in adult life, and increases in the prevalence of intermediate and large oligomeric assembly states are associated with both ageing and Alzheimer's disease. Selective intraneuronal amyloid-β accumulation in adult life and oligomerization during the ageing process are potential contributors to the degeneration of basal forebrain cholinergic neurons in Alzheimer's disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
    Brain 03/2015; 138(6). DOI:10.1093/brain/awv024 · 9.20 Impact Factor
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    • "However, chemical flocculants are difficult to degrade, harmful to humans and thus pose threat to environment. Aluminum, a major component of chemical flocculants, has been found to induce Alzheimer's disease (Master et al., 1985). In contrast, bioflocculants produced by microorganisms during their growth are biodegradable polymers and are safe for ecosystems (Deng et al., 2003). "
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    ABSTRACT: A bioflocculant-producing bacterial isolate designated as ‘TERI-IASST N’ was isolated from activated sludge samples collected from an oil refinery. This isolate demonstrated maximum bioflocculation activity (74%) from glucose among 15 different bioflocculant-producing bacterial strains isolated from the sludge samples and identified as Achromobacter sp. based on 16S rRNA gene sequence. Optimization of pH and supplementation of urea as nitrogen source in the production medium enhanced the flocculation activity of strain TERI-IASST N to 84% (at pH 6). This strain revealed maximum flocculation activity (90%) from sucrose compared to the flocculation activity observed from other carbon sources as investigated (glucose, lactose, fructose, maltose and starch). Ca2+ served as the suitable divalent cation for maximum bioflocculation activity of TERI-IASST strain N. Maximum flocculation activity was observed at optimum C/N ratio of 1. Flocculation activity of this strain decreased to 75% in the presence of heavy metals; Zn, Pb, Ni, Cu and Cd. In addition strain N revealed considerable biosorption of Zn (430 mg L−1) and Pb (30 mg L−1). Bioflocculant yield of strain N was 10.5 g L−1. Fourier transform infrared spectrum indicated the presence of carboxyl, hydroxyl, and amino groups, typical of glycoprotein. Spectroscopic analysis of bioflocculant by nuclear magnetic resonance revealed that it is a glycoprotein, consisting of 57% total sugar and 13% protein.
    Chemosphere 10/2014; 113:116–124. DOI:10.1016/j.chemosphere.2014.04.050 · 3.34 Impact Factor
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