Extracellular vesicle-associated aβ mediates trans-neuronal bioenergetic and ca2+-handling deficits in alzheimer’s disease models

npj Aging and Mechanisms of Disease

Volumn 2, Issue 1, 2016, Pages

  Eitan, Erez ^a   Hutchison, Emmette R ^a   Marosi, Krisztina ^a   Comotto, James ^a   Mustapic, Maja ^a   Nigam, Saket M ^a   Suire, Caitlin ^a   Maharana, Chinmoyee ^a   Jicha, Gregory A ^b   Liu, Dong ^a   Machairaki, Vasiliki ^c   Witwer, Kenneth W ^c   Kapogiannis, Dimitrios ^a   Mattson, Mark P ^a,c  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85052669954     PISSN: None     EISSN: 20563973     Source Type: Journal    
DOI: 10.1038/npjamd.2016.19     Document Type: Article

References (76)

1. Mattson, M. P. Pathways towards and away from Alzheimer's disease. Nature 430, 631–639 (2004).
2. Karch, C. M., Cruchaga, C. & Goate, A. M. Alzheimer's disease genetics: from the bench to the clinic. Neuron 83, 11–26 (2014).
3. Platt, T. L., Reeves, V. L. & Murphy, M. P. Transgenic models of Alzheimer's disease: better utilization of existing models through viral transgenesis. Biochim. Biophys. Acta 1832, 1437–1448 (2013).
4. Bezprozvanny, I. & Mattson, M. P. Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease. Trends Neurosci. 31, 454–463 (2008).
5. Stutzmann, G. E. & Mattson, M. P. Endoplasmic reticulum Ca(2+) handling in excitable cells in health and disease. Pharmacol. Rev. 63, 700–727 (2011).
6. Mattson, M. P., Gleichmann, M. & Cheng, A. Mitochondria in neuroplasticity and neurological disorders. Neuron 60, 748–766 (2008).
7. Crews, L. & Masliah, E. Molecular mechanisms of neurodegeneration in Alzheimer's disease. Hum. Mol. Genet. 19, R12–R20 (2010).
8. Krstic, D. & Knuesel, I. Deciphering the mechanism underlying late-onset Alzheimer disease. Nat. Rev. Neurol. 9, 25–34 (2013).
9. Aguzzi, A. & Rajendran, L. The transcellular spread of cytosolic amyloids, prions, and prionoids. Neuron 64, 783–790 (2009).
10. Watts, J. C. et al. Serial propagation of distinct strains of Abeta prions from Alzheimer's disease patients. Proc. Natl Acad. Sci. USA 111, 10323–10328 (2014).
11. Stohr, J. et al. Purified and synthetic Alzheimer's amyloid beta (Abeta) prions. Proc. Natl Acad. Sci. USA 109, 11025–11030 (2012).
12. Colombo, E., Borgiani, B., Verderio, C. & Furlan, R. Microvesicles: novel biomarkers for neurological disorders. Front. Physiol. 3, 63 (2012).
13. Rajendran, L. et al. Emerging roles of extracellular vesicles in the nervous system. J. Neurosci. 34, 15482–15489 (2014).
14. Rajendran, L. et al. Alzheimer's disease beta-amyloid peptides are released in association with exosomes. Proc. Natl Acad. Sci. USA 103, 11172–11177 (2006).
15. Perez-Gonzalez, R., Gauthier, S. A., Kumar, A. & Levy, E. The exosome secretory pathway transports amyloid precursor protein carboxyl-terminal fragments from the cell into the brain extracellular space. J. Biol. Chem. 287, 43108–43115 (2012).
16. Saman, S. et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J. Biol. Chem. 287, 3842–3849 (2012).
17. Emmanouilidou, E. et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J. Neurosci. 30, 6838–6851 (2010).
18. Grad, L. I. et al. Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and-independent mechanisms. Proc. Natl Acad. Sci. USA 111, 3620–3625 (2014).
19. Fevrier, B. et al. Cells release prions in association with exosomes. Proc. Natl Acad. Sci. USA 101, 9683–9688 (2004).
20. Rajendran, L. et al. Increased Abeta production leads to intracellular accumulation of Abeta in flotillin-1-positive endosomes. Neurodegener. Dis. 4, 164–170 (2007).
21. Colombo, M., Raposo, G. & Thery, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30, 255–289 (2014).
22. Takahashi, R. H. et al. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am. J. Pathol. 161, 1869–1879 (2002).
23. Yuyama, K., Sun, H., Mitsutake, S. & Igarashi, Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-beta by microglia. J. Biol. Chem. 287, 10977–10989 (2012).
24. Yuyama, K. et al. Decreased amyloid-beta pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J. Biol. Chem. 289, 24488–24498 (2014).
25. Yuyama, K. et al. A potential function for neuronal exosomes: sequestering intracerebral amyloid-beta peptide. FEBS Lett. 589, 84–88 (2015).
26. An, K. et al. Exosomes neutralize synaptic-plasticity-disrupting activity of Abeta assemblies in vivo. Mol. Brain 6, 47 (2013).
27. Fiandaca, M. S. et al. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement. 11, 600–7.e1 (2014).
28. Wolfe, D. M. et al. Autophagy failure in Alzheimer's disease and the role of defective lysosomal acidification. Eur. J. Neurosci. 37, 1949–1961 (2013).
29. Witwer, K. W. et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell Vesicles 2 (2013).
30. Lotvall, J. et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J. Extracell Vesicles 3, 26913 (2014).
31. Spies, P. E. et al. The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of Alzheimer's disease from non-Alzheimer's dementia. Curr. Alzheimer Res. 7, 470–476 (2010).
32. Sauvee, M. et al. Additional use of Abeta(4)(2)/Abeta(4)(0) ratio with cerebrospinal fluid biomarkers P-tau and Abeta(4)(2) increases the level of evidence of Alzheimer's disease pathophysiological process in routine practice. J. Alzheimers Dis. 41, 377–386 (2014).
33. Mahairaki, V. et al. Induced pluripotent stem cells from familial Alzheimer's disease patients differentiate into mature neurons with amyloidogenic properties. Stem Cells Dev. 23, 2996–3010 (2014).
34. Bulloj, A., Leal, M. C., Xu, H., Castano, E. M. & Morelli, L. Insulin-degrading enzyme sorting in exosomes: a secretory pathway for a key brain amyloid-beta degrading protease. J. Alzheimers Dis. 19, 79–95 (2010).
35. Ghidoni, R. et al. Cystatin C is released in association with exosomes: a new tool of neuronal communication which is unbalanced in Alzheimer's disease. Neurobiol. Aging 32, 1435–1442 (2011).
36. Yuyama, K., Yamamoto, N. & Yanagisawa, K. Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation. J. Neurochem. 105, 217–224 (2008).
37. Thinakaran, G. & Koo, E. H. Amyloid precursor protein trafficking, processing, and function. J. Biol. Chem. 283, 29615–29619 (2008).
38. Vingtdeux, V. et al. Intracellular pH regulates amyloid precursor protein intracellular domain accumulation. Neurobiol. Dis. 25, 686–696 (2007).
39. Haass, C., Capell, A., Citron, M., Teplow, D. B. & Selkoe, D. J. The vacuolar H (+)-ATPase inhibitor bafilomycin A1 differentially affects proteolytic processing of mutant and wild-type beta-amyloid precursor protein. J. Biol. Chem. 270, 6186–6192 (1995).
40. Mattson, M. P. et al. beta-Amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J. Neurosci. 12, 376–389 (1992).
41. Xin, H. et al. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J. Cereb. Blood Flow Metab. 33, 1711–1715 (2013).
42. Borchelt, D. R. et al. Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19, 939–945 (1997).
43. Oddo, S. et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 39, 409–421 (2003).
44. Dumurgier, J. et al. Cerebrospinal fluid amyloid-beta 42/40 ratio in clinical setting of memory centers: a multicentric study. Alzheimers Res. Ther. 7, 30 (2015).
45. Kuperstein, I. et al. Neurotoxicity of Alzheimer's disease Abeta peptides is induced by small changes in the Abeta42 to Abeta40 ratio. EMBO J. 29, 3408–3420 (2010).
46. Pauwels, K. et al. Structural basis for increased toxicity of pathological abeta42: abeta40 ratios in Alzheimer disease. J. Biol Chem. 287, 5650–5660 (2012).
47. Fiandaca, M. S. et al. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement. 11, 600–607 e601 (2015).
48. Kokubo, H. et al. Oligomeric proteins ultrastructurally localize to cell processes, especially to axon terminals with higher density, but not to lipid rafts in Tg2576 mouse brain. Brain Res. 1045, 224–228 (2005).
49. Williamson, R., Usardi, A., Hanger, D. P. & Anderton, B. H. Membrane-bound beta-amyloid oligomers are recruited into lipid rafts by a fyn-dependent mechanism. FASEB J. 22, 1552–1559 (2008).
50. Rushworth, J. V. & Hooper, N. M. Lipid rafts: linking Alzheimer's Amyloid-beta production, aggregation, and toxicity at neuronal membranes. Int. J. Alzheimers Dis. 2011, 603052 (2010).
51. Evangelisti, E. et al. Lipid rafts mediate amyloid-induced calcium dyshomeostasis and oxidative stress in Alzheimer's disease. Curr. Alzheimers Res. 10, 143–153 (2013).
52. Laulagnier, K. et al. Mast cell-and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J. 380, 161–171 (2004).
53. Butterfield, D. A., Hensley, K., Harris, M., Mattson, M. & Carney, J. beta-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer's disease. Biochem. Biophys. Res. Commun. 200, 710–715 (1994).
54. Bruce-Keller, A. J. et al. Bcl-2 protects isolated plasma and mitochondrial membranes against lipid peroxidation induced by hydrogen peroxide and amyloid beta-peptide. J. Neurochem. 70, 31–39 (1998).
55. Keller, J. N. et al. Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J. Neurochem. 69, 273–284 (1997).
56. Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K. & Mattson, M. P. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J. Neurosci. 17, 1046–1054 (1997).
57. Mark, R. J., Lovell, M. A., Markesbery, W. R., Uchida, K. & Mattson, M. P. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J. Neurochem. 68, 255–264 (1997).
58. Tamboli, I. Y. et al. Statins promote the degradation of extracellular amyloid {beta}-peptide by microglia via stimulation of exosome-associated insulin-degrading enzyme (IDE) secretion. J. Biol. Chem. 285, 37405–37414 (2010).
59. Pasternak, S. H., Callahan, J. W. & Mahuran, D. J. The role of the endosomal/ lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer's disease: reexamining the spatial paradox from a lysosomal perspective. J. Alzheimers Dis. 6, 53–65 (2004).
60. Shen, B., Wu, N., Yang, J. M. & Gould, S. J. Protein targeting to exosomes/ microvesicles by plasma membrane anchors. J. Biol. Chem. 286, 14383–14395 (2011).
61. Abache, T. et al. The transferrin receptor and the tetraspanin web molecules CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells. J. Cell Biochem. 102, 650–664 (2007).
62. Andreu, Z. & Yanez-Mo, M. Tetraspanins in extracellular vesicle formation and function. Front. Immunol. 5, 442 (2014).
63. Baietti, M. F. et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14, 677–685 (2012).
64. Cataldo, A. M., Hamilton, D. J. & Nixon, R. A. Lysosomal abnormalities in degenerating neurons link neuronal compromise to senile plaque development in Alzheimer disease. Brain Res. 640, 68–80 (1994).
65. Cataldo, A. M. & Nixon, R. A. Enzymatically active lysosomal proteases are associated with amyloid deposits in Alzheimer brain. Proc. Natl Acad. Sci. USA 87, 3861–3865 (1990).
66. Lee, J. H. et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141, 1146–1158 (2010).
67. Nixon, R. A. et al. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J. Neuropathol. Exp. Neurol. 64, 113–122 (2005).
68. Pickford, F. et al. The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J. Clin. Invest. 118, 2190–2199 (2008).
69. Nilsson, P. et al. Abeta secretion and plaque formation depend on autophagy. Cell Rep. 5, 61–69 (2013).
70. Goetzl, E. J. et al. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology 85, 40–47 (2015).
71. Swerdlow, R. H. Alzheimer's disease pathologic cascades: who comes first, what drives what. Neurotox. Res. 22, 182–194 (2012).
72. Mattson, M. P., Barger, S. W., Begley, J. G. & Mark, R. J. Calcium, free radicals, and excitotoxic neuronal death in primary cell culture. Methods Cell Biol. 46, 187–216 (1995).
73. McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 7, 263–269 (2011).
74. Dubois, B. et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 13, 614–629 (2014).
75. Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
76. Eitan, E., Zhang, S., Witwer, K. W. & Mattson, M. P. Extracellular vesicle-depleted fetal bovine and human sera have reduced capacity to support cell growth. J. Extracell Vesicles 4, 26373 (2015).