Increased Levels of Extracellular Microvesicle Markers and Decreased Levels of Endocytic/Exocytic Proteins in the Alzheimer's Disease Brain

Journal of Alzheimer's Disease

Volumn 54, Issue 4, 2016, Pages 1671-1686

  Musunuri, Sravani ^a   Khoonsari, Payam Emami ^b   Mikus, Maria ^c   Wetterhall, Magnus ^d   Häggmark Mänberg, Anna ^c   Lannfelt, Lars ^a   Erlandsson, Anna ^a   Bergquist, Jonas ^a   Ingelsson, Martin ^a   Shevchenko, Ganna ^a   Nilsson, Peter ^c   Kultima, Kim ^b  

^a UPPSALA UNIVERSITY   (Sweden)

^b UPPSALA UNIVERSITY HOSPITAL   (Sweden)

^c ROYAL INSTITUTE OF TECHNOLOGY   (Sweden)

^d GE Healthcare Life Sciences   (Sweden)

Author keywords

Alzheimer's disease; endocytosis; exocytosis; exosomes; extracellular vesicles; immobilized chemistry antibodies; mass spectrometry

Indexed keywords

ANTIBODY; CD9 ANTIGEN; GLIAL FIBRILLARY ACIDIC PROTEIN; HEAT SHOCK PROTEIN 72; PHOSPHATIDYLINOSITOL 5 PHOSPHATE 4 KINASE TYPE 2 ALPHA; SYNAPTOBREVIN 2; TRANSALDOLASE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; AUTOPSY; CLINICAL ARTICLE; CONTROLLED STUDY; ENDOCYTOSIS; EXOCYTOSIS; HUMAN; HUMAN TISSUE; LIQUID CHROMATOGRAPHY; MEMBRANE MICROPARTICLE; NEOCORTEX; NERVOUS SYSTEM INFLAMMATION; NEUROLOGIC DISEASE; NEUROPATHOLOGY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEOMICS; TANDEM MASS SPECTROMETRY; WESTERN BLOTTING; AGED; BRAIN; EXTRACELLULAR FLUID; FEMALE; GENETICS; MALE; METABOLISM; MIDDLE AGED; PATHOLOGY; PHYSIOLOGY; PROTEIN PROTEIN INTERACTION; TRANSPORT VESICLE; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; BRAIN; CELL-DERIVED MICROPARTICLES; ENDOCYTOSIS; EXOCYTOSIS; EXTRACELLULAR FLUID; FEMALE; HUMANS; MALE; MIDDLE AGED; PROTEIN INTERACTION MAPS; TRANSPORT VESICLES;

EID: 84992050726     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-160271     Document Type: Article

References (79)

1. Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, Hebert LE, Hennekens CH, Taylor JO (1989) Prevalence of Alzheimers disease in a community population of older persons. Higher than previously reported. JAMA 262, 2551-2556
2. Hye A, Lynham S, Thambisetty M, Causevic M, Campbell J, Byers HL, Hooper C, Rijsdijk F, Tabrizi SJ, Banner S, ShawCE, FoyC, Poppe M, Archer N, Hamilton G, Powell J, Brown RG, Sham P,Ward M, Lovestone S (2006) Proteomebased plasma biomarkers for Alzheimers disease. Brain 129, 3042-3050
3. Fratiglioni L, De Ronchi D, Aguero-TorresH(1999)Worldwide prevalence and incidence of dementia. Drugs Aging 15, 365-375
4. Forstl H, Kurz A (1999) Clinical features of Alzheimers disease. Eur Arch Psychiatry Clin Neurosci 249, 288-290
5. Davies L, Wolska B, Hilbich C, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL (1988) A4 amyloid protein deposition and the diagnosis of Alzheimers disease: Prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathologic techniques. Neurology 38, 1688-1693
6. AndreasenNC(1997) Linking mind and brain in the study of mental illnesses: A project for a scientific psychopathology. Science 275, 1586-1593
7. Honer WG, Falkai P, Bayer TA, Xie J, Hu L, Li HY, Arango V, Mann JJ, Dwork AJ, Trimble WS (2002) Abnormalities of SNARE mechanism proteins in anterior frontal cortex in severe mental illness. Cereb Cortex 12, 349-356
8. Reddy PH, Mani G, Park BS, Jacques J, Murdoch G, Whetsell W Jr, Kaye J, Manczak M (2005) Differential loss of synaptic proteins in Alzheimers disease: Implications for synaptic dysfunction. J Alzheimers Dis 7, 103-117; discussion 173-180
9. Masliah E, Honer WG, Mallory M, Voigt M, Kushner P, Hansen L, Terry R (1994) Topographical distribution of synaptic-associated proteins in the neuritic plaques of Alzheimers disease hippocampus. Acta Neuropathol 87, 135-142
10. Sze CI, Troncoso JC, Kawas C, Mouton P, Price DL, Martin LJ (1997) Loss of the presynaptic vesicle protein synaptophysin in hippocampus correlates with cognitive decline in Alzheimer disease. J Neuropathol Exp Neurol 56, 933-944
11. Sze CI, Bi H, Kleinschmidt-DeMasters BK, Filley CM, Martin LJ (2000) Selective regional loss of exocytotic presynaptic vesicle proteins in Alzheimers disease brains. J Neurol Sci 175, 81-90
12. SahekiY, De Camilli P (2012) Synaptic vesicle endocytosis. Cold Spring Harb Perspect Biol 4, a005645
13. Harris TW, Schuske K, Jorgensen EM (2001) Studies of synaptic vesicle endocytosis in the nematode C. elegans. Traffic 2, 597-605
14. Wu LG, Hamid E, Shin W, Chiang HC (2014) Exocytosis and endocytosis: Modes, functions, and coupling mechanisms. Annu Rev Physiol 76, 301-331
15. Mulcahy LA, Pink RC, Carter DR (2014) Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles 3, 24641
16. Rajendran L, Honsho M, Zahn TR, Keller P, Geiger KD, Verkade P, Simons K (2006) Alzheimers disease betaamyloid peptides are released in association with exosomes. Proc Natl Acad Sci U S A 103, 11172-11177
17. Wang G, Dinkins M, He Q, Zhu G, Poirier C, Campbell A, Mayer-Proschel M, Bieberich E (2012) Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): Potential mechanism of apoptosis induction in Alzheimer disease (AD). J Biol Chem 287, 21384-21395
18. Gupta A, Pulliam L (2014) Exosomes as mediators of neuroinflammation. J Neuroinflammation 11, 68
19. Lin J, Li J, Huang B, Liu J, Chen X, Chen X-M, Xu Y-M, Huang L-F,Wang X-Z (2015) Exosomes: Novel biomarkers for clinical diagnosis. ScientificWorldJournal 2015, Article ID 657086, 8 pages, 2015. doi:10.1155/2015/657086
20. Properzi F, Logozzi M, Fais S (2013) Exosomes: The future of biomarkers in medicine. Biomark Med 7, 769-778
21. Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, Abner EL, Petersen RC, Federoff HJ, Miller BL, Goetzl EJ (2015) Identification of preclinical Alzheimers disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement 11, 600-607.e601
22. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, Vanbelle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimers Disease (CERAD) 2. Standardization of the Neuropathologic Assessment of Alzheimers Disease. Neurology 41, 479-486
23. Mastro R, Hall M (1999) Protein delipidation and precipitation by tri-n-butylphosphate, acetone, and methanol treatment for isoelectric focusing and two-dimensional gel electrophoresis. Anal Biochem 273, 313-315
24. Wetterhall M, Shevchenko G, Artemenko K, Sjodin MOD, Bergquist J (2011) Analysis of membrane and hydrophilic proteins simultaneously derived from the mouse brain using cloud-point extraction. Anal Bioanal Chem 400, 2827-2836
25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193, 265-275
26. Chambers MC, Maclean B, Burke R, Amodei D, Ruderman DL, Neumann S, Gatto L, Fischer B, Pratt B, Egertson J, Hoff K, Kessner D, Tasman N, Shulman N, Frewen B, Baker TA, Brusniak MY, Paulse C, Creasy D, Flashner L, Kani K, Moulding C, Seymour SL, Nuwaysir LM, Lefebvre B, Kuhlmann F, Roark J, Rainer P, Detlev S, Hemenway T, Huhmer A, Langridge J, Connolly B, Chadick T, Holly K, Eckels J, Deutsch EW, Moritz RL, Katz JE, Agus DB, Mac-Coss M,Tabb DL, Mallick P (2012)Across-platform toolkit for mass spectrometry and proteomics. Nat Biotechnol 30, 918-920
27. Weisser H, Nahnsen S, Grossmann J, Nilse L, Quandt A, Brauer H, Sturm M, Kenar E, Kohlbacher O, Aebersold R, Malmstrom L (2013) An automated pipeline for highthroughput label-free quantitative proteomics. J Proteome Res 12, 1628-1644
28. Sturm M, Bertsch A, Gropl C, Hildebrandt A, Hussong R, Lange E, Pfeifer N, Schulz-Trieglaff O, Zerck A, Reinert K, Kohlbacher O (2008) OpenMS-an open-source software framework for mass spectrometry. BMC Bioinformatics 9, 163
29. Craig R, Beavis RC (2004) TANDEM: Matching proteins with tandem mass spectra. Bioinformatics 20, 1466-1467
30. Geer LY, Markey SP, Kowalak JA, Wagner L, Xu M, Maynard DM, Yang X, Shi W, Bryant SH (2004) Open mass spectrometry search algorithm. J Proteome Res 3, 958-964
31. Nahnsen S, Bertsch A, Rahnenführer J, Nordheim A, Kohlbacher O (2011) Probabilistic consensus scoring improves tandem mass spectrometry peptide identification. J Proteome Res 10, 3332-3343
32. Kultima K, Nilsson A, Scholz B, Rossbach UL, Falth M, Andren PE (2009) Development and evaluation of normalization methods for label-free relative quantification of endogenous peptides. Mol Cell Proteomics 8, 2285-2295
33. Vizcaino JA, Csordas A, del-Toro N, Dianes JA, Griss J, Lavidas I, Mayer G, Perez-Riverol Y, Reisinger F, Ternent T, Xu QW, Wang R, Hermjakob H (2016) 2016 update of the PRIDE database and its related tools. Nucleic Acids Res 44, D447-D456
34. R Core Team (2013) R:Alanguage and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL http://www.R-project.org
35. Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3, Article 3
36. Smyth GK (2005) Limma: Linear models for microarray data. In Bioinformatics and Computational Biology Solutions using R and Bioconductor, Gentleman R, Carey V, Dudoit S, Irizarry R, Huber W, eds. Springer, New York, pp. 397-420
37. Templ M, Kowarik A, Filzmoser P (2011) Iterative stepwise regression imputation using standard and robust methods. Comput Stat Data Anal 55, 2793-2806
38. Smyth GK, Michaud J, Scott HS (2005) Use of withinarray replicate spots for assessing differential expression in microarray experiments. Bioinformatics 21, 2067-2075
39. Silva JC, Gorenstein MV, Li GZ, Vissers JP, Geromanos SJ (2006) Absolute quantification of proteins by LCMSE: A virtue of parallel MS acquisition. Mol Cell Proteomics 5, 144-156
40. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, Jensen LJ (2013) STRING v9.1: Protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41, D808-D815
41. Ayoglu B, Chaouch A, Lochmuller H, Politano L, Bertini E, Spitali P, Hiller M, Niks EH, Gualandi F, Ponten F, Bushby K, Aartsma-Rus A, Schwartz E, Le Priol Y, Straub V, Uhlen M, Cirak S, t Hoen PA, Muntoni F, Ferlini A, Schwenk JM, Nilsson P, Al-Khalili Szigyarto C (2014) Affinity proteomics within rare diseases: A BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med 6, 918-936
42. Bachmann J, Burte F, Pramana S, Conte I, Brown BJ, Orimadegun AE, Ajetunmobi WA, Afolabi NK, Akinkunmi F, Omokhodion S, Akinbami FO, Shokunbi WA, Kampf C, Pawitan Y, Uhlen M, Sodeinde O, Schwenk JM, Wahlgren M, Fernandez-Reyes D, Nilsson P (2014) Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria. PLoS Pathog 10, e1004038
43. Bystrom S, Ayoglu B, Haggmark A, Mitsios N, Hong MG, Drobin K, Forsstrom B, Fredolini C, Khademi M, Amor S, UhlenM,OlssonT, Mulder J, Nilsson P, SchwenkJM(2014) Affinity proteomic profiling of plasma, cerebrospinal fluid, and brain tissue within multiple sclerosis. J Proteome Res 13, 4607-4619
44. Haggmark A, Mikus M, Mohsenchian A, Hong MG, Forsstrom B, Gajewska B, Baranczyk-Kuzma A, Uhlen M, Schwenk JM, Kuzma-Kozakiewicz M, Nilsson P (2014) Plasma profiling reveals three proteins associated to amyotrophic lateral sclerosis. Ann Clin Transl Neurol 1, 544-553
45. Schwenk JM, Gry M, Rimini R, Uhlen M, Nilsson P (2008) Antibody suspension bead arrays within serum proteomics. J Proteome Res 7, 3168-3179
46. Dezfouli M, Vickovic S, Iglesias MJ, Nilsson P, Schwenk JM, Ahmadian A (2014) Magnetic bead assisted labeling of antibodies at nanogram scale. Proteomics 14, 14-18
47. Schoch S, Deak F, Konigstorfer A, Mozhayeva M, Sara Y, Sudhof TC, Kavalali ET (2001) SNARE function analyzed in synaptobrevin/VAMPknockout mice. Science 294, 1117-1122
48. Ungar D, HughsonFM(2003) SNAREprotein structure and function. Annu Rev Cell Dev Biol 19, 493-517
49. Peng L, Liu H, Ruan H, Tepp WH, Stoothoff WH, Brown RH, Johnson EA,YaoWD, Zhang SC, DongM(2013) Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival. Nat Commun 4, 1472
50. Johannes L, Doussau F, Clabecq A, Henry JP, Darchen F, Poulain B (1996) Evidence for a functional link between Rab3 and the SNARE complex. J Cell Sci 109(Pt 12), 2875-2884
51. Beites CL, Xie H, Bowser R, TrimbleWS(1999) The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nat Neurosci 2, 434-439
52. Zhou A, Brewer KD, Rizo J (2013) Analysis of SNARE complex/synaptotagmin-1 interactions by one-dimensional NMR spectroscopy. Biochemistry 52, 3446-3456
53. Leenders AG, Lopes da Silva FH, Ghijsen WE, Verhage M (2001) Rab3a is involved in transport of synaptic vesicles to the active zone in mouse brain nerve terminals. Mol Biol Cell 12, 3095-3102
54. Dulubova I, Lou X, Lu J, Huryeva I, Alam A, Schneggenburger R, Sudhof TC, Rizo J (2005) A Munc13/RIM/Rab3 tripartite complex: From priming to plasticity? EMBO J 24, 2839-2850
55. Verhage M, Maia AS, Plomp JJ, Brussaard AB, Heeroma JH, Vermeer H, Toonen RF, Hammer RE, van den Berg TK, Missler M, Geuze HJ, Sudhof TC (2000) Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 287, 864-869
56. Wang X, Thiagarajan R, Wang Q, Tewolde T, Rich MM, Engisch KL (2008) Regulation of quantal shape by Rab3A: Evidence for a fusion pore-dependent mechanism. J Physiol 586, 3949-3962
57. Toonen RF, Wierda K, Sons MS, de Wit H, Cornelisse LN, Brussaard A, Plomp JJ, Verhage M (2006) Munc18-1 expression levels control synapse recovery by regulating readily releasable pool size. Proc Natl Acad Sci U S A 103, 18332-18337
58. Hondius DC, van Nierop P, Li KW, Hoozemans JJ, van der Schors RC, van Haastert ES, van der Vies SM, Rozemuller AJ, Smit AB (2016) Profiling the human hippocampal proteome at all pathologic stages of Alzheimers disease. Alzheimers Dement 12, 654-668
59. Musunuri S, Wetterhall M, Ingelsson M, Lannfelt L, Artemenko K, Bergquist J, Kultima K, Shevchenko G (2014) Quantification of the brain proteome in Alzheimers disease using multiplexed mass spectrometry. J Proteome Res 13, 2056-2068
60. Zelaya MV, Perez-Valderrama E, de Morentin XM, Tunon T, Ferrer I, Luquin MR, Fernandez-Irigoyen J, Santamaria E (2015) Olfactory bulb proteome dynamics during the progression of sporadic Alzheimers disease: Identification of common and distinct olfactory targets across Alzheimer-related co-pathologies. Oncotarget 6, 39437-39456
61. Heuser J (1980) Three-dimensional visualization of coated vesicle formation in fibroblasts. J Cell Biol 84, 560-583
62. Kasprowicz J, Kuenen S, Miskiewicz K, Habets RL, Smitz L, Verstreken P (2008) Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake. J Cell Biol 182, 1007-1016
63. Tian Y, Chang JC, Fan EY, Flajolet M, Greengard P (2013) Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimers APP-CTF for terminal degradation via autophagy. Proc Natl Acad Sci U S A 110, 17071-17076
64. Owen DJ, Collins BM, Evans PR (2004) Adaptors for clathrin coats: Structure and function. Annu Rev Cell Dev Biol 20, 153-191
65. Antonescu CN, Aguet F, Danuser G, Schmid SL (2011) Phosphatidylinositol-(4,5)-bisphosphate regulates clathrincoated pit initiation, stabilization, and size. Mol Biol Cell 22, 2588-2600
66. Sun Y, Carroll S, Kaksonen M, Toshima JY, Drubin DG (2007) PtdIns(4,5)P2 turnover is required for multiple stages during clathrin-and actin-dependent endocytic internalization. J Cell Biol 177, 355-367
67. Appelqvist H,Waster P, Kagedal K, Ollinger K (2013) The lysosome: From waste bag to potential therapeutic target. J Mol Cell Biol 5, 214-226
68. Nixon RA, Yang DS, Lee JH (2008) Neurodegenerative lysosomal disorders:Acontinuum from development to late age. Autophagy 4, 590-599
69. Sollvander S, Nikitidou E, Brolin R, Soderberg L, Sehlin D, Lannfelt L, Erlandsson A (2016) Accumulation of amyloid-beta by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons. Mol Neurodegener 11, 38
70. Anand PK, Anand E, Bleck CK, Anes E, Griffiths G (2010) Exosomal Hsp70 induces a pro-inflammatory response to foreign particles including mycobacteria. PLoS One 5, e10136
71. Heppner FL, Ransohoff RM, Becher B (2015) Immune attack: The role of inflammation in Alzheimer disease. Nat Rev Neurosci 16, 358-372
72. Stincone A, Prigione A, Cramer T, Wamelink MM, Campbell K, Cheung E, Olin-Sandoval V, Gruning N, Kruger A, Tauqeer Alam M, Keller MA, Breitenbach M, Brindle KM, Rabinowitz JD, RalserM(2015) The return of metabolism: Biochemistry and physiology of the pentose phosphate pathway. Biol Rev Camb Philos Soc 90, 927-963
73. Palmer AM (1999) The activity of the pentose phosphate pathway is increased in response to oxidative stress in Alzheimers disease. J Neural Transm (Vienna) 106, 317-328
74. Chen Z, Zhong C (2013) Decoding Alzheimers disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies. Prog Neurobiol 108, 21-43
75. Prunotto M, Farina A, Lane L, Pernin A, Schifferli J, HochstrasserDF, Lescuyer P, Moll S (2013) Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. J Proteomics 82, 193-229
76. Alberio T, McMahon K, Cuccurullo M, Gethings LA, Lawless C, Zibetti M, Lopiano L, Vissers JP, Fasano M (2014) Verification of a Parkinsons disease protein signature in Tlymphocytes by multiple reaction monitoring. J Proteome Res 13, 3554-3561
77. Dimou L, GotzM(2014) Glial cells as progenitors and stem cells: New roles in the healthy and diseased brain. Physiol Rev 94, 709-737
78. Kato S, Gondo T, Hoshii Y, Takahashi M, Yamada M, Ishihara T (1998) Confocal observation of senile plaques in Alzheimers disease: Senile plaque morphology and relationship between senile plaques and astrocytes. Pathol Int 48, 332-340
79. Ben Haim L, Carrillo-SauvageMA,Ceyzeriat K, Escartin C(2015) Elusive roles for reactive astrocytes in neurodegenerative diseases. Front Cell Neurosci 9, 278