Neurobiology of Aging
Volume 32, Issue 12 , Pages 2211-2218 , December 2011

Aβ oligomers inhibit synapse remodelling necessary for memory consolidation

  • Darragh B. Freir

      Affiliations

    • Laboratory for Neurodegenerative Research, Ireland
    • These authors contributed equally to this work.
    • ,
  • Rocio Fedriani

      Affiliations

    • Applied Neurotherapeutics Research Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    • These authors contributed equally to this work.
    • ,
  • Darren Scully

      Affiliations

    • Applied Neurotherapeutics Research Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    • ,
  • Imelda M. Smith

      Affiliations

    • Laboratory for Neurodegenerative Research, Ireland
    • ,
  • Dennis J. Selkoe

      Affiliations

    • Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA
    • ,
  • Dominic M. Walsh

      Affiliations

    • Laboratory for Neurodegenerative Research, Ireland
    • Corresponding Author InformationCorresponding authors at: The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Tel.: +353 1 7166751; fax: +353 1 7166805.
    • ,
  • Ciaran M. Regan

      Affiliations

    • Applied Neurotherapeutics Research Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
    • Corresponding Author InformationCorresponding authors at: The Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. Tel.: +353 1 7166751; fax: +353 1 7166805.

Received 19 October 2009 ,Revised 22 December 2009 ,Accepted 4 January 2010.

References 

  1. Alexinsky T, Przybyslawski J, Mileusnic R, Rose SP, Sara SJ. Antibody to day-old chick brain glycoprotein produces amnesia in adult rats. Neurobiol. Learn Mem. 1997;67:14–20
  2. Ambrogi Lorenzini CG, Baldi E, Bucherelli C, Sacchetti B, Tassoni G. Role of ventral hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response memory trace. Brain Res. 1997;768:242–248
  3. Bertoni-Freddari C, Fattoretti P, Meier-Ruge W, Ulrich J. Computer-assisted morphometry of synaptic plasticity during aging and dementia. Pathol. Res. Pract. 1989;185:799–802
  4. Calabrese B, Shaked GM, Tabarean IV, Braga J, Koo EH, Halpain S. Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-beta protein. Mol. Cell Neurosci. 2007;35:183–193
  5. Cirrito JR, May PC, O’Dell MA, Taylor JW, Parsadanian M, Cramer JW, et al. In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J. Neurosci. 2003;23:8844–8853
  6. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, et al. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat. Neurosci. 2005;8:79–84
  7. Czerniawski J, Yoon T, Otto T. Dissociating space and trace in dorsal and ventral hippocampus. Hippocampus. 2009;19:20–32
  8. Davies CA, Mann DM, Sumpter PQ, Yates PO. A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. J. Neurol. Sci. 1987;78:151–164
  9. DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann. Neurol. 1990;27:457–464
  10. Doyle E, Nolan PM, Bell R, Regan CM. Intraventricular infusions of anti-neural cell adhesion molecules in a discrete posttraining period impair consolidation of a passive avoidance response in the rat. J. Neurochem. 1992;59:1570–1573
  11. Eyre MD, Richter-Levin G, Avital A, Stewart MG. Morphological changes in hippocampal dentate gyrus synapses following spatial learning in rats are transient. Eur. J. Neurosci. 2003;17:1973–1980
  12. Ferrer I, Gullotta F. Down's syndrome and Alzheimer's disease: dendritic spine counts in the hippocampus. Acta Neuropathol. 1990;79:680–685
  13. Foley AG, Hartz BP, Gallagher HC, Rønn LCB, Berezin V, Bock E, et al. A synthetic peptide ligand of NCAM Ig1 domain prevents NCAM internalization and disrupts passive avoidance learning. J. Neurochem. 2000;74:2607–2613
  14. Fox GB, O’Connell AW, Murphy KJ, Regan CM. Memory consolidation induces a transient and time-dependent increase in the frequency of neural cell adhesion molecule polysialylated cells in the adult rat hippocampus. J. Neurochem. 1995;65:2796–2799
  15. Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, et al. Alzheimer's Disease International: Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366:2112–2117
  16. Gómez-Isla T, Hollister R, West H, Mui S, Growdon JH, Petersen RC, et al. Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease. Ann. Neurol. 1997;41:17–24
  17. Gundersen HJG. Notes on estimation of the numerical density of arbitrary profiles: the edge effect. J. Microsc. 1977;111:219–223
  18. Jacobsen JS, Wu CC, Redwine JM, Comery TA, Arias R, Bowlby M, et al. Early-onset behavioral and synaptic deficits in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. U. S. A. 2006;103:5161–5166
  19. Kidd M. Alzheimer's disease—An electron microscopical study. Brain. 1964;87:307–320
  20. Klein WL, Krafft GA, Finch CE. Targeting small Abeta oligomers: the solution to an Alzheimer's disease conundrum?. Trends Neurosci. 2001;24:219–224
  21. LaCor PN, Buniel MC, Furlow PW, Clemente AS, Velasco PT, Wood M, et al. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer's disease. J. Neurosci. 2007;27:796–807
  22. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, et al. Diffusible, nonfribrillar ligands derived from Aβ1–42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U. S. A. 1998;95:6448–6453
  23. Lamprecht R, LeDoux J. Structural plasticity and memory. Nat. Rev. Neurosci. 2004;5:45–54
  24. Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature. 2006;440:352–357
  25. Malenka RC, Bear MF. LTP and LTD: an embarrassment of riches. Neuron. 2004;44:5–21
  26. Marrone DF. Ultrastructural plasticity associated with hippocampal-dependent learning: A meta-analysis. Neurobiol. Learn. Mem. 2007;87:361–371
  27. Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW, et al. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology. 2001;56:127–129
  28. McDonald, J.M., Savva, G.M., Brayne, C., Welzel, A.T., Shankar, G.M., Selkoe, D.J., Inceand P.G., Walsh, D.M. The presence of SDS-stable Ab dimers is strongly associated with Alzheimer-type dementia. Brain, submitted for publication.
  29. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, et al. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann. Neurol. 1999;46:860–866
  30. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G, et al. High-level neuronal expression of abeta 1–42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J. Neurosci. 2000;20:4050–4058
  31. Nadel L, Land C. Memory traces revisited. Nat. Rev. Neurosci. 2000;1:209–212
  32. Nader K. Memory traces abound. Trends Neurosci. 2003;26:65–72
  33. Nakamura S, Murayama N, Noshita T, Annoura H, Ohno T. Progressive brain dysfunction following intracerebroventricular infusion of beta(1–42)-amyloid peptide. Brain Res. 2001;912:128–136
  34. O’Malley A, O’Connell AW, Regan CM. Ultrastructrural analysis reveals avoidance conditioning to induce a transient increase in hippocampal dentate spine density in the 6 hour post-training period of consolidation. Neuroscience. 1998;87:607–613
  35. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. second ed.. New York: Academic Press; 1986;
  36. Poling A, Morgan-Paisley K, Panos JJ, Kim EM, O’Hare E, Cleary JP, et al. Oligomers of the amyloid-beta protein disrupt working memory: confirmation with two behavioral procedures. Behav. Brain Res. 2008;193:230–234
  37. Rao A, Craig AM. Activity regulates the synaptic localization of the NMDA receptor in hippocampal neurons. Neuron. 1997;19:801–812
  38. Roullet P, Mileusnic R, Rose SP, Sara SJ. Neural cell adhesion molecules play a role in rat memory formation in appetitive as well as aversive tasks. Neuroreport. 1997;8:1907–1911
  39. Scheff SW, Price DA, Schmitt FA, DeKosky ST, Mufson EJ. Synaptic alterations in CA1 in mild Alzheimer disease and mild cognitive impairment. Neurology. 2007;68:1501–1508
  40. Seymour CM, Foley AG, Murphy KJ, Regan CM. Intraventricular infusions of anti-NCAM PSA impair the process of consolidation of both avoidance conditioning and spatial learning paradigms in Wistar rats. Neuroscience. 2008;157:813–820
  41. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci. 2007;27:2866–2875
  42. Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 2008;14:837–842
  43. Shrestha BR, Vitolo OV, Joshi P, Lordkipanidze T, Shelanski M, Dunaevsky A. Amyloid beta peptide adversely affects spine number and motility in hippocampal neurons. Mol. Cell Neurosci. 2006;33:274–282
  44. Sterio DC. The unbiased estimation of number and sizes of arbitrary particles using the disector. J. Microsc. 1984;134:127–136
  45. Sze CI, Troncoso JC, Kawas C, Mouton P, Price DL, Martin LJ. Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J. Neuropathol. Exp. Neurol. 1997;56:933–944
  46. Terry RD. The fine structure of neurofibrillary tangles in Alzheimer's disease. J. Neuropathol. Exp. Neurol. 1963;22:629–642
  47. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 1991;30:572–580
  48. Townsend M, Shankar GM, Mehta T, Walsh DM, Selkoe DJ. Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: a potent role for trimers. J. Physiol. 2006;572:477–492
  49. Trivedi M, Coover G. Lesions of the ventral hippocampus, but not the dorsal hippocampus, impair conditioned fear expression and inhibitory avoidance on the elevated T-maze. Neurobiol. Learn. Mem. 2004;81:172–184
  50. Uylings HB, de Brabander JM. Neuronal changes in normal human aging and Alzheimer's disease. Brain Cogn. 2002;49:268–276
  51. Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ. Detection of intracellular oligomers of amyloid β-protein in cells derived from human brain. Biochemistry. 2000;39:10831–10839
  52. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–539
  53. Walsh DM, Selkoe DJ. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron. 2004;44:181–193
  54. Walsh DM, Townsend M, Podlisny MB, Shankar GM, Fadeeva JV, Agnaf OE, et al. Certain inhibitors of synthetic amyloid beta-peptide (Abeta) fibrillogenesis block oligomerization of natural Abeta and thereby rescue long-term potentiation. J. Neurosci. 2005;25:2455–2462
  55. Walsh DM, Selkoe DJ. Abeta oligomers—a decade of discovery. J. Neurochem. 2007;101:1172–1184
  56. Wang HW, Pasternak JF, Kuo H, Ristic H, Lambert MP, Chromy B, et al. Soluble oligomers of β-amyloid (1–42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res. 2002;924:133–140

PII: S0197-4580(10)00030-8

doi: 10.1016/j.neurobiolaging.2010.01.001

Neurobiology of Aging
Volume 32, Issue 12 , Pages 2211-2218 , December 2011

Article Tools

* Image Usage & Resolution