Alzheimer's disease and Aβ toxicity: from top to bottom

Evidence implicating the β-amyloid protein (Aβ) in the pathogenesis of Alzheimer's disease has steadily accumulated. However, the mechanism by which Aβ causes dementia is unknown. Here we argue that a more integrated, top–down approach to brain function is needed to assess the role of Aβ in Alzheimer's disease, and that more attention should be paid to the effects of Aβ on synaptic function rather than on cell death.

[1]  J J Hopfield,et al.  Neurons with graded response have collective computational properties like those of two-state neurons. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[2]  G K Wilcock,et al.  Anatomical correlates of the distribution of the pathological changes in the neocortex in Alzheimer disease. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[3]  D Purves,et al.  Nerve terminal remodeling visualized in living mice by repeated examination of the same neuron. , 1987, Science.

[4]  D. Mann,et al.  A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease , 1987, Journal of the Neurological Sciences.

[5]  A Treves,et al.  Associative memory neural network with low temporal spiking rates. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Paul J. Harrison,et al.  Distribution of a kainate/AMPA receptor mRNA in normal and Alzheimer brain. , 1990, Neuroreport.

[7]  T. Powell,et al.  A quantitative study of the neurofibrillary tangles and the choline acetyltransferase activity in the cerebral cortex and the amygdala in Alzheimer's disease. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[8]  M. Mattson,et al.  beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  M. Mattson,et al.  Calcium-destabilizing and neurodegenerative effects of aggregated β-amyloid peptide are attenuated by basic FGF , 1993, Brain Research.

[10]  C. Cotman,et al.  Apoptosis is induced by beta-amyloid in cultured central nervous system neurons. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Small,et al.  An Amyloid Peptide, βA4 25–35, Mimics the Function of Substance P on Modulation of Nicotine‐Evoked Secretion and Desensitization in Cultured Bovine Adrenal Chromaffin Cells , 1993, Journal of neurochemistry.

[12]  C. Cotman,et al.  Rapid Communication: Ca2+ Channel Blockers Attenuate β‐Amyloid Peptide Toxicity to Cortical Neurons in Culture , 1994 .

[13]  Y Sakurai,et al.  Involvement of auditory cortical and hippocampal neurons in auditory working memory and reference memory in the rat , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  C. Behl,et al.  Hydrogen peroxide mediates amyloid β protein toxicity , 1994, Cell.

[15]  M. Mattson,et al.  A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  C. Cotman,et al.  Ca2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons in culture. , 1994, Journal of neurochemistry.

[17]  C. Cotman,et al.  Differential Induction of Immediate Early Gene Proteins in Cultured Neurons by β‐Amyloid (Aβ): Association of c‐Jun with Aβ‐Induced Apoptosis , 1995 .

[18]  D. Ferrari,et al.  Activation of microglial cells by β-amyloid protein and interferon-γ , 1995, Nature.

[19]  M. Bear,et al.  Mechanism for a sliding synaptic modification threshold , 1995, Neuron.

[20]  C. Behl,et al.  Amyloid peptides are toxic via a common oxidative mechanism. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Johnston,et al.  Synaptic activation of voltage-gated channels in the dendrites of hippocampal pyramidal neurons. , 1995, Science.

[22]  M. Segal Imaging of calcium variations in living dendritic spines of cultured rat hippocampal neurons. , 1995, The Journal of physiology.

[23]  J A Reggia,et al.  A Neural Model of Memory Impairment in Di(cid:11)use Cerebral Atrophy , 2004 .

[24]  M. Mattson,et al.  Amyloid beta-peptide impairs ion-motive ATPase activities: evidence for a role in loss of neuronal Ca2+ homeostasis and cell death , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  R. Rydel,et al.  Amyloid β‐Mediated Oxidative and Metabolic Stress in Rat Cortical Neurons: No Direct Evidence for a Role for H2O2 Generation , 1996, Journal of neurochemistry.

[26]  J. Loike,et al.  Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils , 1996, Nature.

[27]  Eytan Ruppin,et al.  Neuronal-Based Synaptic Compensation: A Computational Study in Alzheimer's Disease , 1996, Neural Computation.

[28]  X. Chen,et al.  RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease , 1996, Nature.

[29]  G. Schellenberg,et al.  Secreted amyloid β–protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease , 1996, Nature Medicine.

[30]  F. Maxfield,et al.  Microglial Cells Internalize Aggregates of the Alzheimer's Disease Amyloid β-Protein Via a Scavenger Receptor , 1996, Neuron.

[31]  James L. McClelland,et al.  Considerations arising from a complementary learning systems perspective on hippocampus and neocortex , 1996, Hippocampus.

[32]  C. Cotman,et al.  β‐Amyloid Neurotoxicity In Vitro: Evidence of Oxidative Stress but Not Protection by Antioxidants , 1997, Journal of neurochemistry.

[33]  K. Kawasaki,et al.  Amyloid β Protein Potentiates Ca2+ Influx Through L‐Type Voltage‐Sensitive Ca2+ Channels: A Possible Involvement of Free Radicals , 1997, Journal of neurochemistry.

[34]  W. Tourtellotte,et al.  Amyloid-beta peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[35]  S. Estus,et al.  Aggregated Amyloid-β Protein Induces Cortical Neuronal Apoptosis and Concomitant “Apoptotic” Pattern of Gene Induction , 1997, The Journal of Neuroscience.

[36]  J. Kemp,et al.  Inhibition of the electrostatic interaction between beta-amyloid peptide and membranes prevents beta-amyloid-induced toxicity. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. Johnston,et al.  A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons , 1997, Science.

[38]  B. Gilchrest,et al.  Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis. A possible mechanism for Alzheimer's disease. , 1997, The Journal of clinical investigation.

[39]  D. Johnston,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997 .

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

[41]  M. Yeckel,et al.  L-Type calcium channels are required for one form of hippocampal mossy fiber LTP. , 1998, Journal of neurophysiology.

[42]  G. Buzsáki,et al.  Dendritic Spikes Are Enhanced by Cooperative Network Activity in the Intact Hippocampus , 1998, The Journal of Neuroscience.

[43]  E Ruppin,et al.  Neuronal regulation versus synaptic unlearning in memory maintenance mechanisms. , 1998, Network.

[44]  C. Albanese,et al.  Amyloid β-peptide stimulates nitric oxide production in astrocytes through an NFκB-dependent mechanism , 1998 .

[45]  C. Hertel,et al.  β‐amyloid binds to p75NTR and activates NFκB in human neuroblastoma cells , 1998 .

[46]  Eytan Ruppin,et al.  Memory Maintenance via Neuronal Regulation , 1998, Neural Computation.

[47]  Douglas R. McDonald,et al.  b-Amyloid Fibrils Activate Parallel Mitogen-Activated Protein Kinase Pathways in Microglia and THP 1 Monocytes , 1998 .

[48]  David S. Park,et al.  Involvement of Cell Cycle Elements, Cyclin-dependent Kinases, pRb, and E2F·DP, in B-amyloid-induced Neuronal Death* , 1999, The Journal of Biological Chemistry.

[49]  S. B. Kater,et al.  Calcium-dependent alterations in dendritic architecture of hippocampal pyramidal neurons. , 1999, Neuroreport.

[50]  David H. Small,et al.  Alzheimer's Disease and the Amyloid β Protein , 1999 .

[51]  G. Turrigiano Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same , 1999, Trends in Neurosciences.

[52]  M. Frotscher,et al.  Cerebral Amyloid Induces Aberrant Axonal Sprouting and Ectopic Terminal Formation in Amyloid Precursor Protein Transgenic Mice , 1999, The Journal of Neuroscience.

[53]  M. Hasselmo,et al.  Plaque-induced neurite abnormalities: implications for disruption of neural networks in Alzheimer's disease. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[54]  C. Masters,et al.  Exacerbation of Copper Toxicity in Primary Neuronal Cultures Depleted of Cellular Glutathione , 1999, Journal of neurochemistry.

[55]  G. Landreth,et al.  Identification of Microglial Signal Transduction Pathways Mediating a Neurotoxic Response to Amyloidogenic Fragments of β-Amyloid and Prion Proteins , 1999, The Journal of Neuroscience.

[56]  M. Emmerling,et al.  Inhibitors of V‐Type ATPases, Bafilomycin A1 and Concanamycin A, Protect Against β‐Amyloid‐Mediated Effects on 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) Reduction , 1999, Journal of neurochemistry.

[57]  Y. Sakurai How do cell assemblies encode information in the brain? , 1999, Neuroscience & Biobehavioral Reviews.

[58]  S. Estus,et al.  c‐Jun Contributes to Amyloid β‐Induced Neuronal Apoptosis but Is Not Necessary for Amyloid β‐Induced c‐jun Induction , 1999 .

[59]  John J. Hopfield,et al.  Neural networks and physical systems with emergent collective computational abilities , 1999 .

[60]  C. Cotman,et al.  Neuronal Apoptosis Induced by β-Amyloid Is Mediated by Caspase-8 , 1999, Neurobiology of Disease.

[61]  D. Storm,et al.  Making New Connections Role of ERK/MAP Kinase Signaling in Neuronal Plasticity , 1999, Neuron.

[62]  C. Cotman,et al.  Multiple Pathways of Apoptosis in PC12 Cells , 1999, The Journal of Biological Chemistry.

[63]  L. V. Van Eldik,et al.  β-Amyloid Stimulation of Inducible Nitric-oxide Synthase in Astrocytes Is Interleukin-1β- and Tumor Necrosis Factor-α (TNFα)-dependent, and Involves a TNFα Receptor-associated Factor- and NFκB-inducing Kinase-dependent Signaling Mechanism* , 2000, The Journal of Biological Chemistry.

[64]  S. Rabacchi,et al.  Caspase-2 Mediates Neuronal Cell Death Induced by β-Amyloid , 2000, The Journal of Neuroscience.

[65]  Mark C. W. van Rossum,et al.  Stable Hebbian Learning from Spike Timing-Dependent Plasticity , 2000, The Journal of Neuroscience.

[66]  L. Abbott,et al.  Synaptic plasticity: taming the beast , 2000, Nature Neuroscience.

[67]  R. Terry Cell death or synaptic loss in Alzheimer disease. , 2000, Journal of neuropathology and experimental neurology.

[68]  D. Small,et al.  Regulation of APP cleavage by α‐, β‐ and γ‐secretases , 2000 .

[69]  P. A. Peterson,et al.  β-Amyloid1–42 Binds to α7 Nicotinic Acetylcholine Receptor with High Affinity , 2000, The Journal of Biological Chemistry.

[70]  J. Yakel,et al.  b-Amyloid 1 – 42 Peptide Directly Modulates Nicotinic Receptors in the Rat Hippocampal Slice , 2000 .

[71]  S. Nelson,et al.  Hebb and homeostasis in neuronal plasticity , 2000, Current Opinion in Neurobiology.

[72]  David S. Park,et al.  E2F1 Mediates Death of B-amyloid-treated Cortical Neurons in a Manner Independent of p53 and Dependent on Bax and Caspase 3* , 2000, The Journal of Biological Chemistry.

[73]  M. Kawahara,et al.  Alzheimer’s b -Amyloid, Human Islet Amylin, and Prion Protein Fragment Evoke Intracellular Free Calcium Elevations by a Common Mechanism in a Hypothalamic GnRH Neuronal Cell Line* , 2000 .

[74]  J. Leo van Hemmen,et al.  Modeling Synaptic Plasticity in Conjunction with the Timing of Pre- and Postsynaptic Action Potentials , 2000, Neural Computation.

[75]  L. Tsai,et al.  Neurotoxicity induces cleavage of p35 to p25 by calpain , 2000, Nature.

[76]  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.

[77]  B. Sommer,et al.  Amyloid β interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease , 2000, Nature Neuroscience.

[78]  Computational neuroscience at the NIH , 2000, Nature Neuroscience.

[79]  Junying Yuan,et al.  Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β , 2000, Nature.

[80]  Isaac Meilijson,et al.  Effective Neuronal Learning with Ineffective Hebbian Learning Rules , 2001, Neural Computation.

[81]  L. Greene,et al.  β‐Amyloid‐induced neuronal apoptosis requires c‐Jun N‐terminal kinase activation , 2001, Journal of neurochemistry.

[82]  J. David Sweatt,et al.  β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In Vitro and In Vivo Mechanisms Related to Alzheimer's Disease , 2001, The Journal of Neuroscience.

[83]  J. Yakel,et al.  β-Amyloid1–42 Peptide Directly Modulates Nicotinic Receptors in the Rat Hippocampal Slice , 2001, The Journal of Neuroscience.

[84]  I. Ferrer,et al.  Phosphorylated Map Kinase (ERK1, ERK2) Expression is Associated with Early Tau Deposition in Neurones and Glial Cells, but not with Increased Nuclear DNA Vulnerability and Cell Death, in Alzheimer Disease, Pick's Disease, Progressive Supranuclear Palsy and Corticobasal Degeneration , 2001, Brain pathology.

[85]  G. Landreth,et al.  β-Amyloid Stimulation of Microglia and Monocytes Results in TNFα-Dependent Expression of Inducible Nitric Oxide Synthase and Neuronal Apoptosis , 2001, The Journal of Neuroscience.

[86]  L. Maffei,et al.  Requirement of ERK Activation for Visual Cortical Plasticity , 2001, Science.

[87]  H. Shibasaki,et al.  α7 Nicotinic Receptor Transduces Signals to Phosphatidylinositol 3-Kinase to Block A β-Amyloid-induced Neurotoxicity* , 2001, The Journal of Biological Chemistry.

[88]  G. Doucet,et al.  Astrocytes from Cerebral Cortex or Striatum Attract Adult Host Serotoninergic Axons into Intrastriatal Ventral Mesencephalic Co-Grafts , 2001, The Journal of Neuroscience.

[89]  β‐Amyloid‐induced neuronal apoptosis requires c‐Jun N‐terminal kinase activation , 2001, Journal of neurochemistry.

[90]  D. K. Berg,et al.  β-Amyloid peptide blocks the response of α7-containing nicotinic receptors on hippocampal neurons , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[91]  T. Arendt Alzheimer's disease as a disorder of mechanisms underlying structural brain self-organization , 2001, Neuroscience.

[92]  A. Smit,et al.  Synapse Formation between Central Neurons Requires Postsynaptic Expression of the MEN1 Tumor Suppressor Gene , 2001, The Journal of Neuroscience.

[93]  THE ~-AMYLOID PROTEIN OF ALZHEIMER ' S DISEASE , .