Table of Contents
Journal of Neurodegenerative Diseases
Volume 2013, Article ID 657470, 8 pages
http://dx.doi.org/10.1155/2013/657470
Review Article

Amyloid Beta-Protein and Neural Network Dysfunction

Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, UNAM, Campus Juriquilla, Boulevard Juriquilla 3001, 76230 Querétaro, Qro, Mexico

Received 27 October 2012; Accepted 6 December 2012

Academic Editor: Gal Bitan

Copyright © 2013 Fernando Peña-Ortega. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. J. Selkoe, “Alzheimer's disease is a synaptic failure,” Science, vol. 298, no. 5594, pp. 789–791, 2002. View at Publisher · View at Google Scholar · View at Scopus
  2. D. M. Walsh and D. J. Selkoe, “Aβ oligomers: a decade of discovery,” Journal of Neurochemistry, vol. 101, no. 5, pp. 1172–1184, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. L. F. Lue, Y. M. Kuo, A. E. Roher et al., “Soluble amyloid β peptide concentration as a predictor of synaptic change in Alzheimer's disease,” American Journal of Pathology, vol. 155, no. 3, pp. 853–862, 1999. View at Google Scholar · View at Scopus
  4. J. Näslund, V. Haroutunian, R. Mohs et al., “Correlation between elevated levels of amyloid β-peptide in the brain and cognitive decline,” Journal of the American Medical Association, vol. 283, no. 12, pp. 1571–1577, 2000. View at Google Scholar · View at Scopus
  5. I. Benilova, E. Karran, and B. De Strooper, “The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes,” Nature Neuroscience, vol. 15, no. 3, pp. 349–357, 2012. View at Google Scholar
  6. M. Sheng, B. L. Sabatini, and T. C. Südhof, “Synapses and Alzheimer's disease,” Cold Spring Harbor Perspectives in Biology, vol. 4, no. 5, 2012. View at Google Scholar
  7. A. Corbett, J. Smith, and C. Ballard, “New and emerging treatments for Alzheimer's disease,” Expert Review of Neurotherapeutics, vol. 12, no. 5, pp. 535–543, 2012. View at Google Scholar
  8. J. J. Palop and L. Mucke, “Amyloid-β-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks,” Nature Neuroscience, vol. 13, no. 7, pp. 812–818, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. D. W. Wesson, R. A. Nixon, E. Levy, and D. A. Wilson, “Mechanisms of neural and behavioral dysfunction in Alzheimer's disease,” Molecular Neurobiology, vol. 43, no. 3, pp. 163–179, 2011. View at Publisher · View at Google Scholar · View at Scopus
  10. F. Peña, A. I. Gutiérrez-Lerma, R. Quiroz-Baez, and C. Arias, “The role of β-amyloid protein in synaptic function: implications for Alzheimer's disease therapy,” Current Neuropharmacology, vol. 4, no. 2, pp. 149–163, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Faught, “Antiepileptic drug trials, the view from the clinic,” Epileptic Disorders, vol. 14, no. 2, pp. 114–123, 2012. View at Google Scholar
  12. S. A. R. B. Rombouts, R. Goekoop, C. J. Stam, F. Barkhof, and P. Scheltens, “Delayed rather than decreased BOLD response as a marker for early Alzheimer's disease,” NeuroImage, vol. 26, no. 4, pp. 1078–1085, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. D. Prvulovic, V. van de Ven, A. T. Sack, K. Maurer, and D. E. J. Linden, “Functional activation imaging in aging and dementia,” Psychiatry Research, vol. 140, no. 2, pp. 97–113, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. B. Platt, B. Drever, D. Koss et al., “Abnormal cognition, sleep, EEG and brain metabolism in a novel knock-in Alzheimer mouse, PLB1,” PLoS ONE, vol. 6, no. 11, Article ID e27068, 2011. View at Google Scholar
  15. D. H. Small, “Network dysfunction in Alzheimer's disease: does synaptic scaling drive disease progression?” Trends in Molecular Medicine, vol. 14, no. 3, pp. 103–108, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. J. P. Cleary, D. M. Walsh, J. J. Hofmeister et al., “Natural oligomers of the amyloid-β protein specifically disrupt cognitive function,” Nature Neuroscience, vol. 8, no. 1, pp. 79–84, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Lesné, T. K. Ming, L. Kotilinek et al., “A specific amyloid-β protein assembly in the brain impairs memory,” Nature, vol. 440, no. 7082, pp. 352–357, 2006. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Balducci, M. Beeg, M. Stravalaci et al., “Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 5, pp. 2295–2300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. K. A. Kittelberger, F. Piazza, G. Tesco, and L. G. Reijmers, “Natural amyloid-beta oligomers acutely impair the formation of a contextual fear memory in mice,” PLoS ONE, vol. 7, no. 1, Article ID e29940, 2012. View at Google Scholar
  20. E. A. Mugantseva and I. Y. Podolski, “Animal model of Alzheimer's disease: characteristics of EEG and memory,” Central European Journal of Biology, vol. 4, no. 4, pp. 507–514, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. V. Villette, F. Poindessous-Jazat, A. Simon et al., “Decreased rhythmic GABAergic septal activity and memory-associated θ oscillations after hippocampal amyloid-β pathology in the rat,” Journal of Neuroscience, vol. 30, no. 33, pp. 10991–11003, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. V. Villette, F. Poindessous-Jazat, B. Bellessort et al., “A new neuronal target for beta-amyloid peptide in the rat hippocampus,” Neurobiology of Aging, vol. 33, no. 6, pp. 1–14, 2012. View at Google Scholar
  23. R. D. Traub, N. Spruston, I. Soltesz, A. Konnerth, M. A. Whittington, and J. G. R. Jefferys, “Gamma-frequency oscillations: a neuronal population phenomenon, regulated by synaptic and intrinsic cellular processes, and inducing synaptic plasticity,” Progress in Neurobiology, vol. 55, no. 6, pp. 563–575, 1998. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Buzsáki, “Theta oscillations in the hippocampus,” Neuron, vol. 33, no. 3, pp. 325–340, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. T. Klausberger and P. Somogyi, “Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations,” Science, vol. 321, no. 5885, pp. 53–57, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. J. M. Ramirez, A. K. Tryba, and F. Peña, “Pacemaker neurons and neuronal networks: an integrative view,” Current Opinion in Neurobiology, vol. 14, no. 6, pp. 665–674, 2004. View at Publisher · View at Google Scholar · View at Scopus
  27. M. K. Sun and D. L. Alkon, “Impairment of hippocampal CA1 heterosynaptic transformation and spatial memory by β-amyloid 25–35,” Journal of Neurophysiology, vol. 87, no. 5, pp. 2441–2449, 2002. View at Google Scholar · View at Scopus
  28. J. E. Driver, C. Racca, M. O. Cunningham et al., “Impairment of hippocampal gamma (γ)-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP),” European Journal of Neuroscience, vol. 26, no. 5, pp. 1280–1288, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. F. Cacucci, M. Yi, T. J. Wills, P. Chapman, and J. O'Keefe, “Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 22, pp. 7863–7868, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. M. A. Busche, G. Eichhoff, H. Adelsberger et al., “Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease,” Science, vol. 321, no. 5896, pp. 1686–1689, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. A. Busche, X. Chen, H. A. Henning et al., “Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 22, pp. 8740–8745, 2012. View at Google Scholar
  32. R. Minkeviciene, S. Rheims, M. B. Dobszay et al., “Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy,” Journal of Neuroscience, vol. 29, no. 11, pp. 3453–3462, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. Y. Wang, G. Zhang, H. Zhou, A. Barakat, and H. Querfurth, “Opposite effects of low and high doses of Aβ42 on electrical network and neuronal excitability in the rat prefrontal cortex,” PLoS ONE, vol. 4, no. 12, Article ID e8366, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Peña, B. Ordaz, H. Balleza-Tapia et al., “Beta-amyloid protein (25-35) disrupts hippocampal network activity: role of Fyn-kinase,” Hippocampus, vol. 20, no. 1, pp. 78–96, 2010. View at Publisher · View at Google Scholar · View at Scopus
  35. L. V. Colom, M. T. Castañeda, C. Bañuelos et al., “Medial septal β-amyloid 1-40 injections alter septo-hippocampal anatomy and function,” Neurobiology of Aging, vol. 31, no. 1, pp. 46–57, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. F. Peña-Ortega and R. Bernal-Pedraza, “Amyloid beta peptide slows down sensory-induced hippocampal oscillations,” International Journal of Peptides, vol. 2012, Article ID 236289, 8 pages, 2012. View at Google Scholar
  37. P. J. Uhlhaas and W. Singer, “Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology,” Neuron, vol. 52, no. 1, pp. 155–168, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. M. Bagheri, M. T. Joghataei, S. Mohseni, and M. Roghani, “Genistein ameliorates learning and memory deficits in amyloid β(1-40) rat model of Alzheimer's disease,” Neurobiology of Learning and Memory, vol. 95, no. 3, pp. 270–276, 2011. View at Publisher · View at Google Scholar · View at Scopus
  39. M. Nobakht, S. M. Hoseini, P. Mortazavi et al., “Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease,” Iran Biomedical Journal, vol. 15, no. 1, pp. 51–58, 2011. View at Google Scholar
  40. B. C. Lega, J. Jacobs, and M. Kahana, “Human hippocampal theta oscillations and the formation of episodic memories,” Hippocampus, vol. 22, no. 4, pp. 748–761, 2012. View at Google Scholar
  41. V. S. Sohal, F. Zhang, O. Yizhar, and K. Deisseroth, “Parvalbumin neurons and gamma rhythms enhance cortical circuit performance,” Nature, vol. 459, no. 7247, pp. 698–702, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. J. W. Kowalski, M. Gawel, A. Pfeffer, and M. Barcikowska, “The diagnostic value of EEG in Alzheimer disease: correlation with the severity of mental impairment,” Journal of Clinical Neurophysiology, vol. 18, no. 6, pp. 570–575, 2001. View at Google Scholar · View at Scopus
  43. U. Schreiter-Gasser, T. Gasser, and P. Ziegler, “Quantitative EEG analysis in early onset Alzheimer's disease: correlations with severity, clinical characteristics, visual EEG and CCT,” Electroencephalography and Clinical Neurophysiology, vol. 90, no. 4, pp. 267–272, 1994. View at Publisher · View at Google Scholar · View at Scopus
  44. F. Nobili, F. Copello, P. Vitali et al., “Timing of disease progression by quantitative EEG in Alzheimer's patients,” Journal of Clinical Neurophysiology, vol. 16, no. 6, pp. 566–573, 1999. View at Google Scholar · View at Scopus
  45. R. Ihl, T. Dierks, E. M. Martin, L. Frölich, and K. Maurer, “Topography of the maximum of the amplitude of EEG frequency bands in dementia of the Alzheimer type,” Biological Psychiatry, vol. 39, no. 5, pp. 319–325, 1996. View at Publisher · View at Google Scholar · View at Scopus
  46. C. Babiloni, G. B. Frisoni, M. Pievani et al., “Hippocampal volume and cortical sources of EEG alpha rhythms in mild cognitive impairment and Alzheimer disease,” NeuroImage, vol. 44, no. 1, pp. 123–135, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. K. D. Harris, J. Csicsvari, H. Hirase, G. Dragoi, and G. Buzsáki, “Organization of cell assemblies in the hippocampus,” Nature, vol. 424, no. 6948, pp. 552–556, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Wang, S. Ikonen, K. Gurevicius, T. van Groen, and H. Tanila, “Alteration of cortical EEG in mice carrying mutated human APP transgene,” Brain Research, vol. 943, no. 2, pp. 181–190, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Jyoti, A. Plano, G. Riedel, and B. Platt, “EEG, activity, and sleep architecture in a transgenic AβPP swe/PSEN1A246E Alzheimer's disease mouse,” Journal of Alzheimer's Disease, vol. 22, no. 3, pp. 873–887, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Scott, J. Feng, T. Kiss et al., “Age-dependent disruption in hippocampal theta oscillation in amyloid-β overproducing transgenic mice,” Neurobiology of Aging, vol. 33, no. 7, pp. 13–23, 2012. View at Google Scholar
  51. H. Balleza-Tapia, A. Huanosta-Gutiérrez, A. Márquez-Ramos, N. Arias, and F. Peña, “Amyloid β oligomers decrease hippocampal spontaneous network activity in an age-dependent manner,” Current Alzheimer Research, vol. 7, no. 5, pp. 453–462, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. T. D. R. Cummins, M. Broughton, and S. Finnigan, “Theta oscillations are affected by amnestic mild cognitive impairment and cognitive load,” International Journal of Psychophysiology, vol. 70, no. 1, pp. 75–81, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Adaya-Villanueva, B. Ordaz, H. Balleza-Tapia, A. Márquez-Ramos, and F. Peña-Ortega, “Beta-like hippocampal network activity is differentially affected by amyloid beta peptides,” Peptides, vol. 31, no. 9, pp. 1761–1766, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. J. Shin, “Theta rhythm heterogeneity in humans,” Clinical Neurophysiology, vol. 121, no. 3, pp. 456–457, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. J. Shin, D. Kim, R. Bianchi, R. K. S. Wong, and H. S. Shin, “Genetic dissection of theta rhythm heterogeneity in mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 50, pp. 18165–18170, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. C. Nerelius, A. Sandegren, H. Sargsyan et al., “α-helix targeting reduces amyloid-β peptide toxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 23, pp. 9191–9196, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. F. Peña-Ortega, A. Solis-Cisneros, B. Ordaz, H. Balleza-Tapia, and J. J. López-Guerrero, “Amyloid beta 1-42 inhibits entorhinal cortex activity in the beta-gamma range: role of GSK-3,” Current Alzheimer Research, vol. 9, no. 7, pp. 857–863, 2012. View at Google Scholar
  58. J. P. Wisor, D. M. Edgar, J. Yesavage et al., “Sleep and circadian abnormalities in a transgenic mouse model of Alzheimer's disease: a role for cholinergic transmission,” Neuroscience, vol. 131, no. 2, pp. 375–385, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Akay, K. Wang, Y. M. Akay, A. Dragomir, and J. Wu, “Nonlinear dynamical analysis of carbachol induced hippocampal oscillations in mice,” Acta Pharmacologica Sinica, vol. 30, no. 6, pp. 859–867, 2009. View at Publisher · View at Google Scholar · View at Scopus
  60. L. Verret, E. O. Mann, G. B. Hang et al., “Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model,” Cell, vol. 149, no. 3, pp. 708–721, 2012. View at Google Scholar
  61. D. Hermann, M. Both, U. Ebert et al., “Synaptic transmission is impaired prior to plaque formation in amyloid precursor protein-overexpressing mice without altering behaviorally-correlated sharp wave-ripple complexes,” Neuroscience, vol. 162, no. 4, pp. 1081–1090, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. P. E. Cramer, J. R. Cirrito, D. W. Wesson et al., “ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models,” Science, vol. 335, no. 6075, pp. 1503–1506, 2012. View at Publisher · View at Google Scholar
  63. D. W. Wesson, A. H. Borkowski, G. E. Landreth, R. A. Nixon, E. Levy, and D. A. Wilson, “Sensory network dysfunction, behavioral impairments, and their reversibility in an Alzheimer's β-amyloidosis mouse model,” Journal of Neuroscience, vol. 31, no. 44, pp. 15962–15971, 2011. View at Google Scholar
  64. L. V. Colom, “Septal networks: relevance to theta rhythm, epilepsy and Alzheimer's disease,” Journal of Neurochemistry, vol. 96, no. 3, pp. 609–623, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. L. Carrillo-Reid, F. Tecuapetla, D. Tapia et al., “Encoding network states by striatal cell assemblies,” Journal of Neurophysiology, vol. 99, no. 3, pp. 1435–1450, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. R. N. Leão, L. V. Colom, L. Borgius, O. Kiehn, and A. Fisahn, “Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons,” Neurobiology of Aging, vol. 33, no. 9, pp. 2046–2061, 2012. View at Google Scholar
  67. Y. Rui, R. Li, Y. Liu et al., “Acute effect of β amyloid on synchronized spontaneous Ca2+ oscillations in cultured hippocampal networks,” Cell Biology International, vol. 30, no. 9, pp. 733–740, 2006. View at Publisher · View at Google Scholar · View at Scopus
  68. R. Rönicke, M. Mikhaylova, S. Rönicke et al., “Early neuronal dysfunction by amyloid β oligomers depends on activation of NR2B-containing NMDA receptors,” Neurobiology of Aging, vol. 32, no. 12, pp. 2219–2228, 2011. View at Google Scholar
  69. S. F. Santos, N. Pierrot, N. Morel, P. Gailly, C. Sindic, and J. N. Octave, “Expression of human amyloid precursor protein in rat cortical neurons inhibits calcium oscillations,” Journal of Neuroscience, vol. 29, no. 15, pp. 4708–4718, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. J. Fuentealba, A. Dibarrart, F. Saez-Orellana et al., “Synaptic silencing and plasma membrane dyshomeostasis induced by amyloid-β peptide are prevented by Aristotelia chilensis enriched extract,” Journal of Alzheimers Disease, vol. 31, no. 4, pp. 879–889, 2012. View at Publisher · View at Google Scholar
  71. P. Görtz, J. Opatz, M. Siebler, S. A. Funke, D. Willbold, and C. Lange-Asschenfeldt, “Transient reduction of spontaneous neuronal network activity by sublethal amyloid β (1-42) peptide concentrations,” Journal of Neural Transmission, vol. 116, no. 3, pp. 351–355, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. J. J. Palop, J. Chin, E. D. Roberson et al., “Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease,” Neuron, vol. 55, no. 5, pp. 697–711, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. E. D. Roberson, B. Halabisky, J. W. Yoo et al., “Amyloid-β/fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of alzheimer's disease,” Journal of Neuroscience, vol. 31, no. 2, pp. 700–711, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. S. Ziyatdinova, K. Gurevicius, N. Kutchiashvili et al., “Spontaneous epileptiform discharges in a mouse model of Alzheimer's disease are suppressed by antiepileptic drugs that block sodium channels,” Epilepsy Research, vol. 94, no. 1-2, pp. 75–85, 2011. View at Publisher · View at Google Scholar · View at Scopus
  75. K. Gurevicius, A. Lipponen, and H. Tanila, “Increased cortical and thalamic excitability in freely moving appswe/Ps1de9 mice modeling epileptic activity associated with Alzheimer's disease,” Cerebral Cortex. In press.
  76. J. T. Brown, J. C. Richardson, G. L. Collingridge, A. D. Randall, and C. H. Davies, “Synaptic transmission and synchronous activity is disrupted in hippocampal slices taken from aged TAS10 mice,” Hippocampus, vol. 15, no. 1, pp. 110–117, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. F. Peña and R. Tapia, “Relationships among seizures, extracellular amino acid changes, and neurodegeneration induced by 4-aminopyridine in rat hippocampus: a microdialysis and electroencephalographic study,” Journal of Neurochemistry, vol. 72, no. 5, pp. 2006–2014, 1999. View at Publisher · View at Google Scholar · View at Scopus
  78. F. Peña and N. Alavez-Pérez, “Epileptiform activity induced by pharmacologic reduction of M-current in the developing hippocampus in vitro,” Epilepsia, vol. 47, no. 1, pp. 47–54, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. F. Peña, J. Bargas, and R. Tapia, “Paired pulse facilitation is turned into paired pulse depression in hippocampal slices after epilepsy induced by 4-aminopyridine in vivo,” Neuropharmacology, vol. 42, no. 6, pp. 807–812, 2002. View at Publisher · View at Google Scholar · View at Scopus
  80. F. J. Sepúlveda, C. Opazo, and L. G. Aguayo, “Alzheimer β-amyloid blocks epileptiform activity in hippocampal neurons,” Molecular and Cellular Neuroscience, vol. 41, no. 4, pp. 420–428, 2009. View at Publisher · View at Google Scholar · View at Scopus
  81. P. E. Sanchez, L. Zhu, L. Verret et al., “Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 42, pp. 2895–2903, 2012. View at Google Scholar
  82. R. O. Sanchez-Mejia, J. W. Newman, S. Toh et al., “Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease,” Nature Neuroscience, vol. 11, no. 11, pp. 1311–1318, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. H. Balleza-Tapia and F. Peña, “Pharmacology of the intracellular pathways activated by amyloid beta protein,” Mini-Reviews in Medicinal Chemistry, vol. 9, no. 6, pp. 724–740, 2009. View at Publisher · View at Google Scholar · View at Scopus