Amyloid oligomers: formation and toxicity of Aβ oligomers

Alzheimer’s disease (AD) is an age‐related, progressive degenerative disorder that is characterized by synapse and neuron loss in the brain and the accumulation of protein‐containing deposits (referred to as ‘senile plaques’) and neurofibrillary tangles. Insoluble amyloid β‐peptide (Aβ) fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. However, accumulating evidence suggests that prefibrillar soluble Aβ oligomers induce AD‐related synaptic dysfunction. The size of Aβ oligomers is distributed over a wide molecular weight range (from < 10 kDa to > 100 kDa), with structural polymorphism in Aβ oligomers of similar sizes. Recent studies have demonstrated that Aβ can accumulate in living cells, as well as in extracellular spaces. This review summarizes current research on Aβ oligomers, focusing on their structures and toxicity mechanism. We also discuss possible formation mechanisms of intracellular and extracellular Aβ oligomers.

[1]  K. Ono,et al.  Structure–neurotoxicity relationships of amyloid β-protein oligomers , 2009, Proceedings of the National Academy of Sciences.

[2]  D. Steel,et al.  Determination of the oligomer size of amyloidogenic protein beta-amyloid(1-40) by single-molecule spectroscopy. , 2009, Biophysical journal.

[3]  C. Robinson,et al.  Amyloid-β protein oligomerization and the importance of tetramers and dodecamers in the aetiology of Alzheimer's disease. , 2009, Nature chemistry.

[4]  R. Morimoto,et al.  Biological and chemical approaches to diseases of proteostasis deficiency. , 2009, Annual review of biochemistry.

[5]  G. Zamponi.  Faculty Opinions recommendation of Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. , 2009 .

[6]  M. Staufenbiel,et al.  Memory deficits in APP23/Abca1+/− mice correlate with the level of Aβ oligomers , 2009, ASN neuro.

[7]  John W. Gilbert,et al.  Cellular Prion Protein Mediates Impairment of Synaptic Plasticity by Amyloid-β Oligomers , 2009, Nature.

[8]  D. Teplow,et al.  Amyloid β-Protein Assembly and Alzheimer Disease* , 2009, Journal of Biological Chemistry.

[9]  W. Klein,et al.  Protection of synapses against Alzheimer's-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomers , 2009, Proceedings of the National Academy of Sciences.

[10]  M. Lindgren,et al.  Prefibrillar transthyretin oligomers and cold stored native tetrameric transthyretin are cytotoxic in cell culture. , 2008, Biochemical and biophysical research communications.

[11]  M. Maeda,et al.  Formation of highly toxic soluble amyloid beta oligomers by the molecular chaperone prefoldin , 2008, The FEBS journal.

[12]  M. Lösche,et al.  Soluble amyloid beta-oligomers affect dielectric membrane properties by bilayer insertion and domain formation: implications for cell toxicity. , 2008, Biophysical journal.

[13]  F. LaFerla,et al.  Aβ inhibits the proteasome and enhances amyloid and tau accumulation , 2008, Neurobiology of Aging.

[14]  Robin K. Lammi,et al.  Monitoring the earliest amyloid-beta oligomers via quantized photobleaching of dye-labeled peptides. , 2008, Analytical biochemistry.

[15]  C. Glabe.  Structural Classification of Toxic Amyloid Oligomers* , 2008, Journal of Biological Chemistry.

[16]  Richard W. Clarke,et al.  Direct characterization of amyloidogenic oligomers by single-molecule fluorescence , 2008, Proceedings of the National Academy of Sciences.

[17]  E. Masliah,et al.  Mechanisms of Hybrid Oligomer Formation in the Pathogenesis of Combined Alzheimer's and Parkinson's Diseases , 2008, PloS one.

[18]  L. Juliano,et al.  Amyloid-β Binds to the Extracellular Cysteine-rich Domain of Frizzled and Inhibits Wnt/β-Catenin Signaling* , 2008, Journal of Biological Chemistry.

[19]  K. Yuyama,et al.  Accelerated release of exosome‐associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1‐induced amyloid fibril formation , 2008, Journal of neurochemistry.

[20]  A. Draguhn,et al.  Amyloid β Oligomers (Aβ1–42 Globulomer) Suppress Spontaneous Synaptic Activity by Inhibition of P/Q-Type Calcium Currents , 2008, The Journal of Neuroscience.

[21]  W. Klein,et al.  Amyloid beta oligomers induce impairment of neuronal insulin receptors , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  D. Selkoe,et al.  Soluble Aβ Inhibits Specific Signal Transduction Cascades Common to the Insulin Receptor Pathway* , 2007, Journal of Biological Chemistry.

[23]  J. Rain,et al.  von Hippel–Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step , 2007, Proceedings of the National Academy of Sciences.

[24]  K. Yanagisawa.  Role of gangliosides in Alzheimer's disease. , 2007, Biochimica et biophysica acta.

[25]  Kim N. Green,et al.  Intracellular amyloid-β in Alzheimer's disease , 2007, Nature Reviews Neuroscience.

[26]  M. D'Andrea,et al.  Aβ peptides can enter the brain through a defective blood–brain barrier and bind selectively to neurons , 2007, Brain Research.

[27]  W. Klein,et al.  Aβ Oligomers Induce Neuronal Oxidative Stress through an N-Methyl-D-aspartate Receptor-dependent Mechanism That Is Blocked by the Alzheimer Drug Memantine* , 2007, Journal of Biological Chemistry.

[28]  R. Kayed,et al.  Small Molecule Inhibitors of Aggregation Indicate That Amyloid β Oligomerization and Fibrillization Pathways Are Independent and Distinct* , 2007, Journal of Biological Chemistry.

[29]  Bernardo L Sabatini,et al.  Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway , 2007, The Journal of Neuroscience.

[30]  D. Selkoe,et al.  Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide , 2007, Nature Reviews Molecular Cell Biology.

[31]  S. Maeda,et al.  A Ganglioside-induced Toxic Soluble Aβ Assembly , 2007, Journal of Biological Chemistry.

[32]  M. Maeda,et al.  Localization of prefoldin interaction sites in the hyperthermophilic group II chaperonin and correlations between binding rate and protein transfer rate. , 2006, Journal of molecular biology.

[33]  Hiroshi Kimura,et al.  Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state , 2006, Nature Cell Biology.

[34]  J. Frydman,et al.  The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions , 2006, Nature Cell Biology.

[35]  F. Hartl,et al.  Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. , 2006, Molecular cell.

[36]  R. Nixon.  Autophagy in neurodegenerative disease: friend, foe or turncoat? , 2006, Trends in Neurosciences.

[37]  J. Pettegrew,et al.  Interaction between Aβ Peptide and α Synuclein: Molecular Mechanisms in Overlapping Pathology of Alzheimer’s and Parkinson’s in Dementia with Lewy Body Disease , 2006, Neurochemical Research.

[38]  E. Coulson,et al.  Does the p75 neurotrophin receptor mediate Aβ‐induced toxicity in Alzheimer's disease? , 2006, Journal of neurochemistry.

[39]  D. Small,et al.  High resolution scanning tunnelling microscopy of the beta-amyloid protein (Abeta1-40) of Alzheimer's disease suggests a novel mechanism of oligomer assembly. , 2006, Journal of structural biology.

[40]  S. Maiti,et al.  Selective destabilization of soluble amyloid β oligomers by divalent metal ions , 2006 .

[41]  C. Dobson,et al.  Protein misfolding, functional amyloid, and human disease. , 2006, Annual review of biochemistry.

[42]  P. Lansbury,et al.  Are amyloid diseases caused by protein aggregates that mimic bacterial pore-forming toxins? , 2006, Quarterly Reviews of Biophysics.

[43]  P. Hough,et al.  High-resolution Atomic Force Microscopy of Soluble Aβ42 Oligomers , 2006 .

[44]  C. Almeida,et al.  β-Amyloid Accumulation Impairs Multivesicular Body Sorting by Inhibiting the Ubiquitin-Proteasome System , 2006, The Journal of Neuroscience.

[45]  Mark Bowlby,et al.  Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Gallagher,et al.  A specific amyloid-β protein assembly in the brain impairs memory , 2006, Nature.

[47]  I. Mook‐Jung,et al.  Amyloid peptide attenuates the proteasome activity in neuronal cells , 2005, Mechanisms of Ageing and Development.

[48]  C. Chiamulera,et al.  The expression of p75 neurotrophin receptor protects against the neurotoxicity of soluble oligomers of beta-amyloid. , 2005, Experimental cell research.

[49]  E. Conway de Macario,et al.  Sick chaperones, cellular stress, and disease. , 2005, The New England journal of medicine.

[50]  M. Okochi,et al.  Facilitated release of substrate protein from prefoldin by chaperonin , 2005, FEBS letters.

[51]  M. Okochi,et al.  Kinetics and Binding Sites for Interaction of the Prefoldin with a Group II Chaperonin , 2004, Journal of Biological Chemistry.

[52]  P. Lansbury,et al.  Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. , 2003, Annual review of neuroscience.

[53]  C. Finch,et al.  Self-assembly of Aβ1-42 into globular neurotoxins , 2003 .

[54]  B. Hyman,et al.  Demonstration by FRET of BACE interaction with the amyloid precursor protein at the cell surface and in early endosomes , 2003, Journal of Cell Science.

[55]  X. Roucou,et al.  p75 Neurotrophin Receptor Protects Primary Cultures of Human Neurons against Extracellular Amyloid β Peptide Cytotoxicity , 2003, The Journal of Neuroscience.

[56]  Kazuki Sato,et al.  Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[57]  Carl W. Cotman,et al.  Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis , 2003, Science.

[58]  W. K. Cullen,et al.  Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo , 2002, Nature.

[59]  F. Hartl,et al.  Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein , 2002, Science.

[60]  A. LeBlanc,et al.  Selective cytotoxicity of intracellular amyloid β peptide1–42 through p53 and Bax in cultured primary human neurons , 2002, The Journal of cell biology.

[61]  Brett Chromy,et al.  Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus , 2002, Brain Research.

[62]  T. Morgan,et al.  Vaccination with soluble Aβ oligomers generates toxicity‐neutralizing antibodies , 2001, Journal of neurochemistry.

[63]  Makoto Hashimoto,et al.  β-Amyloid peptides enhance α-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[64]  D. Selkoe.  Alzheimer's disease: genes, proteins, and therapy. , 2001, Physiological reviews.

[65]  C. Finch,et al.  Targeting small Aβ oligomers: the solution to an Alzheimer's disease conundrum? , 2001, Trends in Neurosciences.

[66]  M. Kawahara,et al.  Molecular mechanism of neurodegeneration induced by Alzheimer’s β-amyloid protein: channel formation and disruption of calcium homeostasis , 2000, Brain Research Bulletin.

[67]  D. Selkoe,et al.  The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. , 2000, Biochemistry.

[68]  W. W. Jong,et al.  The Molecular Chaperone aB-crystallin Enhances Amyloid Neurotoxicity , 1999 .

[69]  A. Yang,et al.  Loss of endosomal/lysosomal membrane impermeability is an early event in amyloid Aβ1‐42 pathogenesis , 1998, Journal of neuroscience research.

[70]  J. Vandekerckhove,et al.  Prefoldin, a Chaperone that Delivers Unfolded Proteins to Cytosolic Chaperonin , 1998, Cell.

[71]  T. Morgan,et al.  Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[72]  Xi Chen,et al.  An intracellular protein that binds amyloid-β peptide and mediates neurotoxicity in Alzheimer's disease , 1997, Nature.

[73]  Steven A. Johnson,et al.  Clusterin (apoJ) Alters the Aggregation of Amyloid β-Peptide (Aβ1-42) and Forms Slowly Sedimenting Aβ Complexes That Cause Oxidative Stress , 1995, Experimental Neurology.

[74]  S. Squazzo,et al.  Aggregation of Secreted Amyloid -Protein into Sodium Dodecyl Sulfate-stable Oligomers in Cell Culture (*) , 1995, The Journal of Biological Chemistry.

[75]  T. Holzman,et al.  Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths. , 1994, Biophysical journal.

[76]  J. Hardy,et al.  Alzheimer's disease: the amyloid cascade hypothesis. , 1992, Science.

[77]  Mark A. Smith,et al.  Faculty of 1000 evaluation for Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. , 2012 .

[78]  S. Maeda,et al.  A ganglioside-induced toxic soluble Abeta assembly. Its enhanced formation from Abeta bearing the Arctic mutation. , 2007, The Journal of biological chemistry.

[79]  F. LaFerla,et al.  Intracellular amyloid-beta in Alzheimer's disease. , 2007, Nature reviews. Neuroscience.

[80]  S. Ferreira,et al.  Soluble protein oligomers as emerging toxins in alzheimer's and other amyloid diseases , 2007, IUBMB life.

[81]  Michela Gallagher,et al.  A specific amyloid-beta protein assembly in the brain impairs memory. , 2006, Nature.

[82]  J. Pettegrew,et al.  Interaction between Abeta peptide and alpha synuclein: molecular mechanisms in overlapping pathology of Alzheimer's and Parkinson's in dementia with Lewy body disease. , 2006, Neurochemical research.

[83]  S. Maiti,et al.  Selective destabilization of soluble amyloid beta oligomers by divalent metal ions. , 2006, Biochemical and biophysical research communications.

[84]  P. Muchowski,et al.  Modulation of neurodegeneration by molecular chaperones , 2005, Nature Reviews Neuroscience.

[85]  C. Finch,et al.  Self-assembly of Abeta(1-42) into globular neurotoxins. , 2003, Biochemistry.

[86]  Kazuki Sato,et al.  Spherical aggregates of beta-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3beta. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[87]  Claudio Soto,et al.  Unfolding the role of protein misfolding in neurodegenerative diseases , 2003, Nature Reviews Neuroscience.

[88]  M. Kirkitadze,et al.  Amyloid beta -protein (Abeta) assembly: Abeta 40 and Abeta 42 oligomerize through distinct pathways. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[89]  W Blaine Stine,et al.  Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. , 2002, Brain research.

[90]  Yves-Alain Barde,et al.  The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. , 2002, Nature neuroscience.

[91]  T. Tabira,et al.  Apoptotic neurons in Alzheimer's disease frequently show intracellular Abeta42 labeling. , 2001, Journal of Alzheimer's disease : JAD.

[92]  W. D. de Jong,et al.  The molecular chaperone alphaB-crystallin enhances amyloid beta neurotoxicity. , 1999, Biochemical and biophysical research communications.

[93]  M. Emmerling,et al.  Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. , 1996, The Journal of biological chemistry.

[94]  W. B. Stine,et al.  Clusterin (apoJ) alters the aggregation of amyloid beta-peptide (A beta 1-42) and forms slowly sedimenting A beta complexes that cause oxidative stress. , 1995, Experimental neurology.

[95]  D. Teplow,et al.  Amyloid beta-protein assembly and Alzheimer disease. , 2022 .