Cellular and Molecular Life Sciences

, Volume 71, Issue 24, pp 4803–4813 | Cite as

Amyloid beta receptors responsible for neurotoxicity and cellular defects in Alzheimer’s disease

Review

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Although a major cause of AD is the accumulation of amyloid-β (Aβ) peptide that induces neuronal loss and cognitive impairments, our understanding of its neurotoxic mechanisms is limited. Recent studies have identified putative Aβ-binding receptors that mediate Aβ neurotoxicity in cells and models of AD. Once Aβ interacts with a receptor, a toxic signal is transduced into neurons, resulting in cellular defects including endoplasmic reticulum stress and mitochondrial dysfunction. In addition, Aβ can also be internalized into neurons through unidentified Aβ receptors and induces malfunction of subcellular organelles, which explains some part of Aβ neurotoxicity. Understanding the neurotoxic signaling initiated by Aβ-receptor binding and cellular defects provide insight into new therapeutic windows for AD. In the present review, we summarize the findings on Aβ-binding receptors and the neurotoxicity of oligomeric Aβ.

Keywords

Amyloid beta Alzheimer’s disease Aβ receptor Neurotoxicity Uptake Mitochondria ER stress 

References

  1. 1.
    Kojro E, Fahrenholz F (2005) The non-amyloidogenic pathway: structure and function of alpha-secretases. Subcell Biochem 38:105–127PubMedGoogle Scholar
  2. 2.
    Haass C (2004) Take five-BACE and the γ-secretase quartet conduct Alzheimer’s amyloid β-peptide generation. EMBO J 23(3):483–488PubMedCentralPubMedGoogle Scholar
  3. 3.
    Bertram L, Tanzi RE (2008) Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 9(10):768–778PubMedGoogle Scholar
  4. 4.
    Qi-Takahara Y, Morishima-Kawashima M, Tanimura Y, Dolios G, Hirotani N, Horikoshi Y, Kametani F, Maeda M, Saido TC, Wang R, Ihara Y (2005) Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-secretase. J Neurosci 25(2):436–445PubMedGoogle Scholar
  5. 5.
    Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356PubMedGoogle Scholar
  6. 6.
    Cruts M, Dermaut B, Rademakers R, Van den Broeck M, Stögbauer F, Van Broeckhoven C (2003) Novel APP mutation V715A associated with presenile Alzheimer’s disease in a German family. J Neurol 250(11):1374–1375PubMedGoogle Scholar
  7. 7.
    Suárez-Calvet M, Belbin O, Pera M, Badiola N, Magrané J, Guardia-Laguarta C, Muñoz L, Colom-Cadena M, Clarimón J, Lleó A (2014) Autosomal-dominant Alzheimer’s disease mutations at the same codon of amyloid precursor protein differentially alter Aβ production. J Neurochem 128(2):330–339PubMedGoogle Scholar
  8. 8.
    Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid β-peptide. Nat Rev Mol Cell Biol 8(2):101–112PubMedGoogle Scholar
  9. 9.
    Ahmed M, Davis J, Aucoin D, Sato T, Ahuja S, Aimoto S, Elliott JI, Van Nostrand WE, Smith SO (2010) Structural conversion of neurotoxic amyloid-β1-42 oligomers to fibrils. Nat Struct Mol Biol 17(5):561–567PubMedCentralPubMedGoogle Scholar
  10. 10.
    Ryan DA, Narrow WC, Federoff HJ, Bowers WR (2010) An improved method for generating consistent soluble amyloid-beta oligomer preparations for in vitro neurotoxicity studies. J Neurosci Methods 190(2):171–179PubMedCentralPubMedGoogle Scholar
  11. 11.
    Kumar S, Rezaei-Ghaleh N, Terwel D, Thal DR, Richard M, Hoch M, Mc Donald JM, Wüllner U, Glebov K, Heneka MT, Walsh DM, Zweckstetter M, Walter J (2011) Extracellular phosphorylation of the amyloid β-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer’s disease. EMBO J 30(11):2255–2265PubMedCentralPubMedGoogle Scholar
  12. 12.
    Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, Rönicke R, Reymann K, Hutter-Paier B, Alexandru A, Jagla W, Graubner S, Glabe CG, Demuth HU, Bloom GS (2013) Prion-like behavior and tau-dependent cytotoxicity of pyroglutamylated β-amyloid. Nautre 485(7400):651–655Google Scholar
  13. 13.
    Deshpande A, Kawai H, Metherate R, Glabe CG, Busciglio J (2009) A role for synaptic zinc in activity-dependent Abeta oligomer formation and accumulation at excitatory synapses. J Neurosci 29(13):4004–4015PubMedGoogle Scholar
  14. 14.
    Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ (2011) Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors. J Neurosci 31(18):6627–6638PubMedCentralPubMedGoogle Scholar
  15. 15.
    Lesné S, Koh MT, Ktilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid-β protein assembly in the brain impairs memory. Nature 440(7082):352–357PubMedGoogle Scholar
  16. 16.
    Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, Brett FM, Farrell MA, Rowan MJ, Lemere CA, Regan CM, Walsh DM, Sabatini BL, Selkoe DJ (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14(8):837–842PubMedCentralPubMedGoogle Scholar
  17. 17.
    Bhatia R, Lin H, Lal R (2000) Fresh and globular amyloid beta protein (1-42) induces rapid cellular degeneration: evidence for AbetaP channel-mediated cellular toxicity. FASEB J 14(9):1233–1243PubMedGoogle Scholar
  18. 18.
    Kawahara M, Negishi-Kato M, Sadakane Y (2009) Calcium dyshomeostasis and neurotoxicity of Alzheimer’s beta-amyloid protein. Expert Rev Neurother 9(5):681–693PubMedGoogle Scholar
  19. 19.
    Arispe N, Pollard HB, Rojas E (1993) Giant multilevel cation channels formed by Alzheimer disease amyloid β-protein [AβP-(1-40)] in bilayer membranes. Proc Natl Acad Sci USA 90(22):10573–10577PubMedCentralPubMedGoogle Scholar
  20. 20.
    Inoue S (2008) In situ Aβ pores in AD brain are cylindrical assembly of Aβ protofilaments. Amyloid 15(4):223–233PubMedGoogle Scholar
  21. 21.
    Demuro A, Mina E, Kayed R, Milton SC, Parker I, Glabe CG (2005) Calcium dysregulation and membrane disruption as a ubiquitous neurotoxic mechanism of soluble amyloid oligomers. J Biol Chem 280(17):17294–17300PubMedGoogle Scholar
  22. 22.
    Cowburn RF, Wiehager B, Trief E, Li-Li M, Sundstrom E (1997) Effects of beta-amyloid-(25-35) peptides on radioligand binding to excitatory amino acid receptors and voltage-dependent calcium channels: evidence for a selective affinity for the glutamate and glycine recognition sites of the NMDA receptor. Neurochem Res 22(12):1437–1442PubMedGoogle Scholar
  23. 23.
    Wang HY, Lee DH, D’Andrea MR, Peterson PA, Shank RP, Reitz AB (2000) beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer’s disease pathology. J Biol Chem 275(8):5626–5632PubMedGoogle Scholar
  24. 24.
    Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Morser J, Migheli A, Nawroth P, Stern D, Schmidt AM (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature 382(6593):685–691PubMedGoogle Scholar
  25. 25.
    Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers. Nature 457(7233):1128–1132PubMedCentralPubMedGoogle Scholar
  26. 26.
    Cisse M, Halabisky B, Harris J, Devidze N, Dubal DB, Sun B, Orr A, Lotz G, Kim DH, Hamto P, Ho K, Yu GQ, Mucke L (2011) Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature 469(7328):47–52PubMedCentralPubMedGoogle Scholar
  27. 27.
    Kam TI, Song S, Gwon Y, Park H, Yan JJ, Im I, Choi JW, Choi TY, Kim J, Song DK, Takai T, Kim YC, Kim KS, Choi SY, Choi S, Klein WL, Yuan J, Jung YK (2013) FcgammaRIIb mediates amyloid-beta neurotoxicity and memory impairment in Alzheimer’s disease. J Clin Invest 123(7):2791–2802PubMedCentralPubMedGoogle Scholar
  28. 28.
    Kim T, Vidal GS, Djurisic M, William CM, Birnbaum ME, Garcia KC, Hyman BT, Shatz CJ (2013) Human LilrB2 is a beta-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer’s model. Science 341(6152):1399–1404PubMedGoogle Scholar
  29. 29.
    Schmidt AM, Yan SD, Yan SF, Stern DM (2001) The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 108(7):949–955PubMedCentralPubMedGoogle Scholar
  30. 30.
    Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, Munch G (2011) Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol Aging 32(5):763–777PubMedGoogle Scholar
  31. 31.
    Deane R, Du Yan S, Submamaryan RK, LaRue B, Jovanovic S, Hogg E, Welch D, Manness L, Lin C, Yu J, Zhu H, Ghiso J, Frangione B, Stern A, Schmidt AM, Armstrong DL, Arnold B, Liliensiek B, Nawroth P, Hofman F, Kindy M, Stern D, Zlokovic B (2003) RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain. Nat Med 9(7):907–913PubMedGoogle Scholar
  32. 32.
    Jeynes B, Provias J (2008) Evidence for altered LRP/RAGE expression in Alzheimer lesion pathogenesis. Curr Alzheimer Res 5(5):432–437PubMedGoogle Scholar
  33. 33.
    Sasaki N, Fukatsu R, Tsuzuki K, Hayashi Y, Yoshida T, Fujii N, Koike T, Wakayama I, Yanagihara R, Garruto R, Amano N, Makita Z (1998) Advanced glycation end products in Alzheimer’s disease and other neurodegenerative disease. Am J Pathol 153(4):1149–1155PubMedCentralPubMedGoogle Scholar
  34. 34.
    Arancio O, Zhang HP, Chen X, Lin C, Trinchese F, Puzzo D, Liu S, Hegde A, Yan SF, Stern A, Luddy JS, Lue LF, Walker DG, Roher A, Buttini M, Mucke L, Li W, Schmidt AM, Kindy M, Hyslop PA, Stern DM, Du Yan SS (2004) RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J 23(20):4096–4105PubMedCentralPubMedGoogle Scholar
  35. 35.
    Chen X, Walker DG, Schmidt AM, Arancio O, Lue LF, Yan SD (2007) RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer’s disease. Curr Mol Med 7(8):735–742PubMedGoogle Scholar
  36. 36.
    Deane R, Singh I, Sagare AP, Bell RD, Ross NT, LaRue B, Love R, Perry S, Paquette N, Deane RJ, Thiyagarajan M, Zarcone T, Fritz G, Friedman AE, Miller BL, Zlokovic BV (2012) A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer’s disease. J Clin Invest 122(4):1377–1392PubMedCentralPubMedGoogle Scholar
  37. 37.
    Galasko D, Bell J, Mancuso JY, Kupiec JW, Sabbagh MN, van Dyck C, Thomas RG, Aisen PS (2014) Clinical trial of an inhibitor of RAGE-Aβ interactions in Alzheimer disease. Neurology 82(17):1536–1542PubMedGoogle Scholar
  38. 38.
    Costa RO, Lacor PN, Ferreira IL, Resende R, Auberson YP, Klein WL, Oliveira CR, Rego AC, Pereira CM (2012) Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-D-aspartate receptor in mature hippocampal cultures treated with amyloid-beta oligomers. Aging Cell 11(5):823–833PubMedGoogle Scholar
  39. 39.
    De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, Klein WL (2007) Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 282(15):11590–11601PubMedGoogle Scholar
  40. 40.
    Alberdi E, Sanchez-Gomez MV, Cavaliere F, Perez-Samartin A, Zugaza JL, Trullas R, Domercq M, Matute C (2010) Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium 47(3):264–272PubMedGoogle Scholar
  41. 41.
    Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL (2007) Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 27(11):2866–2875PubMedGoogle Scholar
  42. 42.
    Ronicke R, Mikhaylova M, Ronicke S, Meinhardt J, Schroder UH, Fandrich M, Reiser G, Kreutz MR, Reymann KG (2011) Early neuronal dysfunction by amyloid beta oligomers depends on activation of NR2B-containing NMDA receptors. Neurobiol Aging 32(12):2219–2228PubMedGoogle Scholar
  43. 43.
    Decker H, Jurgensen S, Adrover MF, Brito-Moreira J, Bomfim TR, Klein WL, Epstein AL, De Felice FG, Jerusalinsky D, Ferreira ST (2010) N-methyl-D-aspartate receptors are required for synaptic targeting of Alzheimer’s toxic amyloid-beta peptide oligomers. J Neurochem 115(6):1520–1529PubMedGoogle Scholar
  44. 44.
    Patel AN, Jhamandas JH (2012) Neuronal receptors as targets for the action of amyloid-beta protein (Abeta) in the brain. Expert Rev Mol Med 14:e2PubMedGoogle Scholar
  45. 45.
    Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P (2005) Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 8(8):1051–1058PubMedGoogle Scholar
  46. 46.
    Wang HY, Li W, Benedetti NJ, Lee DH (2003) Alpha 7 nicotinic acetylcholine receptors mediate beta-amyloid peptide-induced tau protein phosphorylation. J Biol Chem 278(34):31547–31553PubMedGoogle Scholar
  47. 47.
    Nagele RG, D’Andrea MR, Anderson WJ, Wang HY (2002) Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer’s disease. Neuroscience 110(2):199–211PubMedGoogle Scholar
  48. 48.
    Dziewczapolski G, Glogowski CM, Masliah E, Heinemann SF (2009) Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer’s disease. J Neurosci 29(27):8805–8815PubMedCentralPubMedGoogle Scholar
  49. 49.
    Hernandez CM, Kayed R, Zheng H, Sweatt JD, Dineley KT (2010) Loss of alpha7 nicotinic receptors enhances beta-amyloid oligomer accumulation, exacerbating early-stage cognitive decline and septohippocampal pathology in a mouse model of Alzheimer’s disease. J Neurosci 30(7):2442–2453PubMedCentralPubMedGoogle Scholar
  50. 50.
    Kudo W, Lee HP, Zou WQ, Wang X, Perry G, Zhu X, Smith MA, Petersen RB, Lee HG (2012) Cellular prion protein is essential for oligomeric amyloid-beta-induced neuronal cell death. Hum Mol Genet 21(5):1138–1144PubMedCentralPubMedGoogle Scholar
  51. 51.
    Freir DB, Nicoll AJ, Klyubin I, Panico S, Mc Donald JM, Risse E, Asante EA, Farrow MA, Sessions RB, Saibil HR, Clarke AR, Rowan MJ, Walsh DM, Collinge J (2011) Interaction between prion protein and toxic amyloid beta assemblies can be therapeutically targeted at multiple sites. Nat Commun 2:336PubMedCentralPubMedGoogle Scholar
  52. 52.
    Barry AE, Klyubin I, Mc Donald JM, Mably AJ, Farrell MA, Scott M, Walsh DM, Rowan MJ (2011) Alzheimer’s disease brain-derived amyloid-beta-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J Neurosci 31(20):7259–7726PubMedGoogle Scholar
  53. 53.
    Gimbel DA, Nygaard HB, Coffey EE, Gunther EC, Lauren J, Gimbel ZA, Strittmatter SM (2010) Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci 30(18):6367–6374PubMedCentralPubMedGoogle Scholar
  54. 54.
    Chung E, Ji Y, Sun Y, Kascsak RJ, Kascsak RB, Mehta PD, Strittmatter SM, Wisniewski T (2010) Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer’s disease model mouse. BMC Neurosci 11:130PubMedCentralPubMedGoogle Scholar
  55. 55.
    Um JW, Nygaard HB, Heiss JK, Kostylev MA, Stagi M, Vortmeyer A, Wisniewski T, Gunther EC, Strittmatter SM (2012) Alzheimer amyloid-beta oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci 15(9):1227–1235PubMedCentralPubMedGoogle Scholar
  56. 56.
    Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, Kerrisk ME, Vortmeyer A, Wisniewski T, Koleske AJ, Gunther EC, Nygaard HB, Strittmatter SM (2013) Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein. Neuron 79(5):887–902PubMedCentralPubMedGoogle Scholar
  57. 57.
    Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wolfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Gotz J (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 142(3):387–397PubMedGoogle Scholar
  58. 58.
    Kessels HW, Nguyen LN, Nabavi S, Malinow R (2010) The prion protein as a receptor for amyloid-beta. Nature 466(7308):E3–E4 discussion E4–5PubMedCentralPubMedGoogle Scholar
  59. 59.
    Calella AM, Farinelli M, Nuvolone M, Mirante O, Moos R, Falsig J, Mansuy IM, Aguzzi A (2010) Prion protein and Abeta-related synaptic toxicity impairment. EMBO Mol Med 2(8):306–314PubMedCentralPubMedGoogle Scholar
  60. 60.
    Cisse M, Sanchez PE, Kim DH, Ho K, Yu GQ, Mucke L (2011) Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice. J Neurosci 31(29):10427–10431PubMedCentralPubMedGoogle Scholar
  61. 61.
    Balducci C, Beeg M, Stravalaci M, Bastone A, Sclip A, Biasini E, Tapella L, Colombo L, Manzoni C, Borsello T, Chiesa R, Gobbi M, Salmona M, Forloni G (2010) Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein. Proc Natl Acad Sci USA 107(5):2295–2300PubMedCentralPubMedGoogle Scholar
  62. 62.
    Fernandez-Vizarra P, Lopez-Franco O, Mallavia B, Higuera-Matas A, Lopez-Parra V, Ortiz-Munoz G, Ambrosio E, Egido J, Almeida OF, Gomez-Guerrero C (2012) Immunoglobulin G Fc receptor deficiency prevents Alzheimer-like pathology and cognitive impairment in mice. Brain 135(Pt 9):2826–2837PubMedGoogle Scholar
  63. 63.
    Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529PubMedGoogle Scholar
  64. 64.
    Han J, Back SH, Hur J, Lin YH, Gildersleeve R, Shan J, Yuan CL, Krokowski D, Wang S, Hatzoglou M, Kilberg MS, Sartor MA, Kaufman RJ (2013) ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol 15(5):481–490PubMedCentralPubMedGoogle Scholar
  65. 65.
    McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ (2001) GADD153 sensitizes cells to endoplasmic reticulum stress by down- regulating BCL2 and perturbing the cellular redox state. Mol Cell Biol 21(4):1249–1259PubMedCentralPubMedGoogle Scholar
  66. 66.
    Shim S, Lee W, Chung H, Jung YK (2011) Amyloid β-induced FOXRED2 mediates neuronal cell death via inhibition of proteasome activity. Cell Mol Life Sci 68(12):2115–2127PubMedGoogle Scholar
  67. 67.
    Huang X, Chen Y, Zhang H, Ma Q, Zhang YW, Xu H (2012) Salubrinal attenuates β-amyloid-induced neuronal death and microglial activation by inhibition of the NF-κB pathway. Neurobiol Aging 33(5):e9–e17PubMedGoogle Scholar
  68. 68.
    Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, Cavener DR, Klann E (2013) Suppression of eIF2α kinases alleviates Alzheimer’s disease-related plasticity and memory deficits. Nat Neurosci 16(9):1299–1305PubMedCentralPubMedGoogle Scholar
  69. 69.
    Michalak M, Robert Parker JM, Opas M (2002) Ca2+ signaling and calcium binding chaperones of the endoplasmic reticulum. Cell Calcium 32(5–6):269–278PubMedGoogle Scholar
  70. 70.
    Chan SL, Mayne M, Holden CP, Geiger JD, Mattson MP (2000) Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons. J Biol Chem 275(24):18195–18200PubMedGoogle Scholar
  71. 71.
    Stutzmann GE, Smith I, Caccamo A, Oddo S, LaFerla FM, Parker I (2006) Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer’s disease mice. J Neurosci 26(19):5180–5189PubMedGoogle Scholar
  72. 72.
    Supnet C, Grant J, Kong H, Westaway D, Mayne M (2006) Amyloid-β-(1-42) increases ryanodine receptor-3 expression and function in neurons of TgCRND8 mice. J Biol Chem 281(50):38440–38447PubMedGoogle Scholar
  73. 73.
    Casas-Tinto S, Zhang Y, Sanchez-Garcia J, Gomez-Velazquez M, Rincon-Limas DE, Fernandez-Funez P (2011) The ER stress factor XBP1 prevents amyloid-β neurotoxicity. Hum Mol Genet 20(11):2144–2160PubMedCentralPubMedGoogle Scholar
  74. 74.
    Demuro A, Parker I (2013) Cytotoxicity of intracellular Aβ42 amyloid oligomers involves Ca2+ release from the endoplasmic reticulum by stimulated production of inositol trisphosphate. J Neurosci 33(9):3824–3833PubMedCentralPubMedGoogle Scholar
  75. 75.
    Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner B, Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β. Nature 403(6765):98–103PubMedGoogle Scholar
  76. 76.
    Sanges D, Comitato A, Tammaro R, Marigo V (2006) Apoptosis in retinal degeneration involves cross-talk between apoptosis-inducing factor (AIF) and caspase-12 and is blocked by calpain inhibitors. Proc Natl Acad Sci USA 103(46):17366–17371PubMedCentralPubMedGoogle Scholar
  77. 77.
    Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276(17):13935–13940PubMedGoogle Scholar
  78. 78.
    Song S, Lee H, Kam TI, Tai ML, Lee JY, Noh JY, Shim SM, Seo SJ, Kong YY, Nakagawa T, Chung CW, Choi DY, Oubrahim H, Jung YK (2008) E2-25K/Hip-2 regulates caspase-12 in ER stress-mediated Aβ neurotoxicity. J Cell Biol 182(4):675–684PubMedCentralPubMedGoogle Scholar
  79. 79.
    Fischer H, Koenig U, Eckhart L, Tschachler E (2002) Human caspase 12 has acquired deleterious mutations. Biochem Biophy Res Comm 293(2):722–726Google Scholar
  80. 80.
    Nishitsuji K, Tomiyama T, Ishibashi K, Ito K, Teraoka R, Lambert MP, Klein WL, Mori H (2009) The E693Δ mutation in amyloid precursor protein increases intracellular accumulation of amyloid β oligomers and causes endoplasmic reticulum stress-induced apoptosis in cultured cells. Am J Pathol 174(3):957–969PubMedCentralPubMedGoogle Scholar
  81. 81.
    Matsuzaki S, Hiratsuka T, Kuwahara R, Katayama T, Tohyama M (2010) Caspase-4 is partially cleaved by calpain via the impairment of Ca2+ homeostasis under the ER stress. Neurochem Int 56(2):352–356PubMedGoogle Scholar
  82. 82.
    Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, Klein WL, Triller A (2010) Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron 66(5):739–754PubMedCentralPubMedGoogle Scholar
  83. 83.
    Pavlov PF, Hansson Petersen C, Glaser E, Ankarcrona M (2009) Mitochondrial accumulation of APP and Abeta: significance for Alzheimer disease pathogenesis. J Cell Mol Med 13(10):4137–4145PubMedGoogle Scholar
  84. 84.
    Casley CS, Canevari L, Land JM, Clark JB, Sharpe MA (2002) Beta-amyloid inhibits integrated mitochondrial respiration and key enzyme activities. J Neurochem 80(1):91–100PubMedGoogle Scholar
  85. 85.
    Gillardon F, Rist W, Kussmaul L, Vogel J, Berg M, Danzer K, Kraut N, Hengerer B (2007) Proteomic and functional alterations in brain mitochondria from Tg2576 mice occur before amyloid plaque deposition. Proteomics 7(4):605–616PubMedGoogle Scholar
  86. 86.
    Crouch PJ, Blake R, Duce JA, Ciccotosto GD, Li QX, Barnham KJ, Curtain CC, Cherny RA, Cappai R, Dyrks T, Masters CL, Trounce IA (2005) Copper-dependent inhibition of human cytochrome c oxidase by a dimeric conformer of amyloid-beta1-42. J Neurosci 25(3):672–679PubMedGoogle Scholar
  87. 87.
    Richards JG, Higgins GA, Ouagazzal AM, Ozmen L, Kew JN, Bohrmann B, Malherbe P, Brockhaus M, Loetscher H, Czech C, Huber G, Bluethmann H, Jacobsen H, Kemp JA (2003) PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation. J Neurosci 23(26):8989–9003PubMedGoogle Scholar
  88. 88.
    Dumont M, Wille E, Stack C, Calingasan NY, Beal MF, Lin MT (2009) Reduction of oxidative stress, amyloid deposition, and memory deficit by manganese superoxide dismutase overexpression in a transgenic mouse model of Alzheimer’s disease. FASEB J 23(8):2459–2466PubMedCentralPubMedGoogle Scholar
  89. 89.
    Perkins GA, Tjong J, Brown JM, Poquiz PH, Scott RT, Kolson DR, Ellisman MH, Spirou GA (2010) The micro-architecture of mitochondria at active zones: electron tomography reveals novel anchoring scaffolds and cristae structured for high-rate metabolism. J Neurosci 30(3):1015–1026PubMedCentralPubMedGoogle Scholar
  90. 90.
    Cai Q, Sheng ZH (2009) Mitochondrial transport and docking in axons. Exp Neurol 218(2):257–267PubMedCentralPubMedGoogle Scholar
  91. 91.
    Saxton WM, Hollenbeck PJ (2012) The axonal transport of mitochondria. J Cell Sci 125(Pt9):2095–2104PubMedCentralPubMedGoogle Scholar
  92. 92.
    Du H, Guo L, Yan S, Sosunov AA, McKhann GM, Yan SS (2010) Early deficits in synaptic mitochondria in an Alzheimer’s disease mouse model. Proc Natl Acad Sci USA 107(43):18670–18675PubMedCentralPubMedGoogle Scholar
  93. 93.
    Wang X, Perry G, Smith MA, Zhu X (2010) Amyloid-beta derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener Dis 7(1–3):56–59PubMedCentralPubMedGoogle Scholar
  94. 94.
    Decker H, Lo KY, Unger SM, Ferreira ST, Silverman MA (2010) Amyloid-β peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3β in primary cultured hippocampal neurons. J Neurosci 30(27):9166–9171PubMedGoogle Scholar
  95. 95.
    Pigino G, Morfini G, Atagi Y, Deshpande A, Yu C, Jungbauer L, LaDu M, Busciglio J, Brady S (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. Proc Natl Acad Sci USA 106(14):5907–5912PubMedCentralPubMedGoogle Scholar
  96. 96.
    Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 29(28):9090–9103PubMedCentralPubMedGoogle Scholar
  97. 97.
    Wang X, Su B, Fujioka H, Zhu X (2008) Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer’s disease patients. Am J Pathol 173(2):470–482PubMedCentralPubMedGoogle Scholar
  98. 98.
    Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA (2009) S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrial fission and neuronal injury. Science 324(5923):102–105PubMedCentralPubMedGoogle Scholar
  99. 99.
    Park SJ, Shin JH, Jeong JI, Song JH, Jo YK, Kim ES, Lee EH, Hwang JJ, Lee EK, Chung SJ, Koh JY, Jo DG, Cho DH (2014) Down-regulation of mortalin exacerbates Aβ-mediated mitochondrial fragmentation and dysfunction. J Biol Chem 289(4):2195–2204PubMedGoogle Scholar
  100. 100.
    DuBoff B, Götz J, Feany MB (2012) Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 75(4):618–632PubMedCentralPubMedGoogle Scholar
  101. 101.
    Grundke-Iqbal I, Iqbal K, George L, Tung YC, Kim KS, Wisniewski HM (1989) Amyloid protein and neurofibrillary tangles coexist in the same neuron in Alzheimer disease. Proc Natl Acad Sci USA 86(8):2853–2857PubMedCentralPubMedGoogle Scholar
  102. 102.
    Takahashi RH, Milner TA, Li F, Nam EE, Edgar MA, Yamaguchi H, Beal MF, Xu H, Greengard P, Gouras GK (2002) Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am J Pathol 161(5):1869–1879PubMedCentralPubMedGoogle Scholar
  103. 103.
    Mori C, Spooner ET, Wisniewsk KE, Wisniewski TM, Yamaguch H, Saido TC, Tolan DR, Selkoe DJ, Lemere CA (2002) Intraneuronal Abeta42 accumulation in down syndrome brain. Amyloid 9(2):88–102PubMedGoogle Scholar
  104. 104.
    Cataldo AM, Petanceska S, Terio NB, Peterhoff CM, Durham R, Mercken M, Mehta PD, Buxbaum J, Haroutunian V, Nixon RA (2004) Abeta localization in abnormal endosomes: association with earliest Abeta elevations in AD and down syndrome. Neurobiol Aging 25(10):1263–1272PubMedGoogle Scholar
  105. 105.
    Wirths O, Multhaup G, Czech C, Blanchard V, Moussaoui S, Tremp G, Pradier L, Beyreuther K, Bayer TA (2001) Intraneuronal Abeta accumulation precedes plaque formation in beta-amyloid precursor protein and presenilin-1 double-transgenic mice. Neurosci Lett 306(1–2):116–120PubMedGoogle Scholar
  106. 106.
    Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39(3):409–421PubMedGoogle Scholar
  107. 107.
    Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26(40):10129–10140PubMedGoogle Scholar
  108. 108.
    Rutten BP, Van der Kolk NM, Schafer S, van Zandvoort MA, Bayer TA, Steinbusch HW, Schmitz C (2005) Age-related loss of synaptophysin immunoreactive presynaptic boutons within the hippocampus of APP751SL, PS1M146L, and APP751SL/PS1M146L transgenic mice. Am J Pathol 167(1):161–173PubMedCentralPubMedGoogle Scholar
  109. 109.
    Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM (2005) Intraneuronal Abeta causes the onset of early Alzheimer’s disease-related cognitive deficits in transgenic mice. Neuron 45(5):675–688PubMedGoogle Scholar
  110. 110.
    Koo EH, Squazzo SL (1994) Evidence that production and release of amyloid beta-protein involves the endocytic pathway. J Biol Chem 269(26):17386–17389PubMedGoogle Scholar
  111. 111.
    Matsuzaki K, Kato K, Yanagisawa K (2010) Abeta polymerization through interaction with membrane gangliosides. Biochim Biophys Acta 1801(8):868–877PubMedGoogle Scholar
  112. 112.
    Kanekiyo T, Zhang J, Liu Q, Liu CC, Zhang L, Bu G (2011) Heparan sulphate proteoglycan and the low-density lipoprotein receptor-related protein 1 constitute major pathways for neuronal amyloid-beta uptake. J Neurosci 31(5):1644–1651PubMedCentralPubMedGoogle Scholar
  113. 113.
    Williamson R, Usardi A, Hanger DP, Anderton BH (2008) Membrane-bound β-amyloid oligomers are recruited into lipid rafts by a fyn-dependent mechanism. FASEB J 22(5):1552–1559PubMedGoogle Scholar
  114. 114.
    Saavedra L, Mohamed A, Ma V, Kar S, de Chaves EP (2007) Internalization of beta-amyloid peptide by primary neurons in the absence of apolipoprotein E. J Biol Chem 282(49):35722–35732PubMedGoogle Scholar
  115. 115.
    Singh TD, Park SY, Bae JS, Yun Y, Bae YC, Park RW, Kim IS (2010) MEGF10 functions as a receptor for the uptake of amyloid-β. FEBS Lett 584(18):3936–3942PubMedGoogle Scholar
  116. 116.
    Fuentealba RA, Liu Q, Zhang J, Kanekiyo T, Hu X, Lee JM, LaDu MJ, Bu G (2010) Low-density lipoprotein receptor-related protein 1 (LRP1) mediates neuronal Abeta42 uptake and lysosomal trafficking. PLoS One 5(7):e11884PubMedCentralPubMedGoogle Scholar
  117. 117.
    Zerbinatti CV, Wahrle SE, Kim H, Cam JA, Bales K, Paul SM, Holtzman DM, Bu G (2006) Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta42 accumulation in amyloid model mice. J Biol Chem 281(47):36180–36186PubMedGoogle Scholar
  118. 118.
    Rushworth JV, Griffiths HH, Watt NT, Hooper NM (2013) Prion protein-mediated toxicity of amyloid-beta oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem 288(13):8935–8951PubMedCentralPubMedGoogle Scholar
  119. 119.
    Takuma K, Fang F, Zhang W, Yan S, Fukuzaki E, Du H, Sosunov A, McKhann G, Funatsu Y, Nakamichi N, Nagai T, Mizoguchi H, Ibi D, Hori O, Ogawa S, Stern DM, Yamada K, Yan SS (2009) RAGE-meidated signaling contributes to intraneuronal transport of amyloid-β and neuronal dysfunction. Proc Natl Acad Sci USA 106(47):20021–20026PubMedCentralPubMedGoogle Scholar
  120. 120.
    Lai AY, McLaurin J (2010) Mechanisms of amyloid-Beta Peptide uptake by neurons: the role of lipid rafts and lipid raft-associated proteins. Int J Alzheimers Dis 2011:548380PubMedCentralPubMedGoogle Scholar
  121. 121.
    Reed-Geaghan EG, Savage JC, Hise AG, Landreth GE (2009) CD14 and Toll-like receptors 2 and 4 are required for fibrillar Aβ-stimulated microglial activation. J Neurosci 29(38):11982–11992PubMedCentralPubMedGoogle Scholar
  122. 122.
    Liu S, Liu Y, Hao W, Wolf L, Kiliaan AJ, Penke B, Rube CE, Walter J, Heneka MT, Hartmann T, Menger MD, Fassbender K (2012) TLR2 is a primary receptor for Alzheimer’s amyloid β peptide to trigger neuroinflammatory activation. J Immunol 188(3):1098–1107PubMedGoogle Scholar
  123. 123.
    Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schuffer W, Fassbender K (2007) Role of the Toll-like receptor 4 in neuroinflammation in Alzheimer’s disease. Cell Physiol Biochem 20(6):947–956PubMedGoogle Scholar
  124. 124.
    Chen K, Iribarren P, Hu J, Chen J, Gong W, Cho EH, Lockett S, Dunlop NM, Wang JM (2006) Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J Biol Chem 281(6):3651–3659PubMedGoogle Scholar
  125. 125.
    Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K (2006) Role of Toll-like receptor signalling in Aβ uptake and clearance. Brain 129(11):3006–3019PubMedCentralPubMedGoogle Scholar
  126. 126.
    Song M, Jin J, Lim JE, Kou J, Pattanayak A, Rehman JA, Kim HD, Tahara K, Lalonde R, Fukuchi K (2011) TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer’s disease. J Neuroinflammation 8:92PubMedCentralPubMedGoogle Scholar
  127. 127.
    Richard KL, Filali M, Prefontaine P, Rivest S (2008) Toll-like receptor 2 acts as a natural innate immune receptor to clear amyloid β1-42 and delay the cognitive decline in a mouse model of Alzheimer’s disease. J Neurosci 28(22):5784–5793PubMedGoogle Scholar
  128. 128.
    Lopez EM, Bell KF, Ribeiro-da-Silva A, Cuello AC (2004) Early changes in neurons of the hippocampus and neocortex in transgenic rats expressing intracellular human a-beta. J Alzheimers Dis 6(4):421–431 discussion 443–429PubMedGoogle Scholar
  129. 129.
    Ditaranto K, Tekirian TL, Yang AJ (2001) Lysosomal membrane damage in soluble Abeta-mediated cell death in Alzheimer’s disease. Neurobiol Dis 8(1):19–31PubMedGoogle Scholar
  130. 130.
    Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Aβ to mitochondrial toxicity in Alzheimer’s disease. Science 304(5699):448–452PubMedGoogle Scholar
  131. 131.
    Du H, Guo L, Fang F, Chen D, Sosunov AA, McKhann GM, Yan Y, Wang C, Zhang H, Molkentin JD, Gunn-Moore FJ, Vonsattel JP, Arancio O, Chen JX, Yan SD (2008) Cyclophilin D deficiency attenuates mitochondrial and neuronal perturbation and ameliorates learning and memory in Alzheimer’s disease. Nat Med 14(10):1097–1105PubMedCentralPubMedGoogle Scholar
  132. 132.
    Almeida CG, Takahashi RH, Gouras GK (2006) β-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neurosci 26(16):4277–4288PubMedGoogle Scholar
  133. 133.
    Ohyagi Y, Asahara H, Chui DH, Tsuruta Y, Sakae N, Miyoshi K, Yamada T, Kikuchi H, Taniwaki T, Murai H, Ikezoe K, Furuya H, Kawarabayashi T, Shoji M, Checler F, Iwaki T, Makifuchi T, Takeda K, Kira J, Tabira T (2005) Intracellular Abeta42 activates p53 promoter: a pathway to neurodegeneration in Alzheimer’s disease. FASEB J 19(2):255–257PubMedGoogle Scholar

Copyright information

© Springer Basel 2014

Authors and Affiliations

  1. 1.Global Research Laboratory, School of Biological SciencesSeoul National UniversitySeoulKorea

Personalised recommendations