Prion diseases are known as neurodegenerative diseases of the central nervous system with a long incubation period. Alzheimer's disease (AD) and prion diseases share the hallmark of severe neuronal loss, although their pathogenic mechanisms are similarly incomplete. It appears that these two neurodegenerative diseases share a complex deterioration of function involved in the onset of neuronal loss. To investigate presymptomatic biochemical changes indicative of the initial stage of prion diseases and decipher the pathophysiological mechanisms of these two neurodegenerative diseases, we performed a differential proteomic analysis on brain tissues of 263K-infected hamsters during the presymptomatic period and transgenic APPSWE, PSEN1dE9 mice (a mouse model of AD). We identified 7 differentially expressed proteins including the β-soluble N-ethylmaleimide-sensitive factor attachment protein (β-SNAP) by 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The β-SNAP expression patterns in the brains of cases and controls were further quantified by Western blotting. β-SNAP showed an early decrease followed by a progressive depletion. The expression of β-SNAP was also significantly downregulated in the mouse model of AD. β-SNAP is brain-specific and known to bind to the SNAP receptors and is therefore involved in the control of neurotransmitter release as well as in constitutive vesicular transport. Our results suggest that presynaptic failure and abnormalities in neurotransmission may be early events in the development of neuronal dysfunction.

1.
Hunter GD: Scrapie: A prototype slow infection. J Infect Dis 1972;125:427-440.
2.
Herbst A, McIlwain S, Schmidt JJ, Aiken JM, Page CD, Li L: Prion disease diagnosis by proteomic profiling. J Proteome Res 2009;8:1030-1036.
3.
Soto C: Diagnosing prion diseases: needs, challenges and hopes. Nat Rev Microbiol 2004;2:809-819.
4.
Ingrosso L, Vetrugno V, Cardone F, Pocchiari M: Molecular diagnostics of transmissible spongiform encephalopathies. Trends Mol Med 2002;8:273-280.
5.
Kordek R: The diagnosis of human prion diseases. Folia Neuropathol 2000;38:151-160.
6.
Porcario C, Hall SM, Martucci F, Corona C, Iulini B, Perazzini AZ, Acutis P, Hamir AN, Loiacono CM, Greenlee JJ, Richt JA, Caramelli M, Casalone C: Evaluation of two sets of immunohistochemical and Western blot confirmatory methods in the detection of typical and atypical BSE cases. BMC Res Notes 2011;4:376.
7.
Bishop MT, Hart P, Aitchison L, Baybutt HN, Plinston C, Thomson V, Tuzi NL, Head MW, Ironside JW, Will RG, Manson JC: Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006;5:393-398.
8.
Ingrosso L, Vetrugno V, Cardone F, Pocchiari M: Molecular diagnostics of transmissible spongiform encephalopathies. Trends Mol Med 2002;8:273-280.
9.
Ma D, Li L: Searching for reliable premortem protein biomarkers for prion diseases: progress and challenges to date. Expert Rev Proteomics 2012;9:267-280.
10.
Sanchez JC, Guillaume E, Lescuyer P, Allard L, Carrette O, Scherl A, Burgess J, Corthals GL, Burkhard PR, Hochstrasser DF: Cystatin C as a potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt-Jakob disease. Proteomics 2004;4:2229-2233.
11.
Perrin RJ, Craig-Schapiro R, Malone JP, Shah AR, Gilmore P, Davis AE, Roe CM, Peskind ER, Li G, Galasko DR, Clark CM, Quinn JF, Kaye JA, Morris JC, Holtzman DM, Townsend RR, Fagan AM: Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease. PLoS One 2011;6:e16032.
12.
Steinacker P, Rist W, Swiatek-de-Lange M, Lehnert S, Jesse S, Pabst A, Tumani H, von Arnim CA, Mitrova E, Kretzschmar HA, Lenter M, Wiltfang J, Otto M: Ubiquitin as potential cerebrospinal fluid marker of Creutzfeldt-Jakob disease. Proteomics 2010;10:81-89.
13.
Piubelli C, Fiorini M, Zanusso G, Milli A, Fasoli E, Monaco S, Righetti PG: Searching for markers of Creutzfeldt-Jakob disease in cerebrospinal fluid by two-dimensional mapping. Proteomics 2006;6(suppl 1):S256-S261.
14.
Keeney JT, Swomley AM, Forster S, Harris JL, Sultana R, Butterfield DA: Apolipoprotein A-I: Insights from redox proteomics for its role in neurodegeneration. Proteomics Clin Appl 2013;7:109-122.
15.
Jucker M, Walker LC: Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 2013;501:45-51.
16.
Morales R, Duran-Aniotz C, Castilla J, Estrada LD, Soto C: De novo induction of amyloid-beta deposition in vivo. Mol Psychiatry 2012;17:1347-1353.
17.
Zhang BY, Tian C, Han J, Gao C, Shi Q, Chen JM, Jiang HY, Zhou W, Dong XP: Establishment of a stable PrPSc panel from brain tissues of experimental hamsters with scrapie strain 263K. Biomed Environ Sci 2009;22:151-156.
18.
Zaborowski A: Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies. Part I (in Polish). Psychiatr Pol 2004;38:283-296.
19.
Meade-White KD, Barbian KD, Race B, Favara C, Gardner D, Taubner L, Porcella S, Race R: Characteristics of 263K scrapie agent in multiple hamster species. Emerg Infect Dis 2009;15:207.
20.
Stenbeck G: Soluble NSF-attachment proteins. Int J Biochem Cell Biol 1998;30:573-577.
21.
Nishiki T, Nihonmatsu I, Tsuhara Y, Kawasaki M, Sekiguchi M, Sato K, Mizoguchi A, Takahashi M: Distribution of soluble N-ethylmaleimide fusion protein attachment proteins (SNAPs) in the rat nervous system. Neuroscience 2001;107:363-371.
22.
Freeman W, Morton AJ: Regional and progressive changes in brain expression of complexin II in a mouse transgenic for the Huntington's disease mutation. Brain Res Bull 2004;63:45-55.
23.
Sandberg M: Calcium dynamics and vesicle-release proteins in a prion-infected neuronal cell line. 2005. http://hdl.handle.net/10616/39011.
24.
Yoo BC, Cairns N, Fountoulakis M, Lubec G: Synaptosomal proteins, beta-soluble N-ethylmaleimide-sensitive factor attachment protein (beta-SNAP), gamma-SNAP and synaptotagmin I in brain of patients with Down syndrome and Alzheimer's disease. Dement Geriatr Cogn Disord 2001;12:219-225.
25.
Zhang C, Wu B, Beglopoulos V, Wines-Samuelson M, Zhang D, Dragatsis I, Sudhof TC, Shen J: Presenilins are essential for regulating neurotransmitter release. Nature 2009;460:632-636.
26.
Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I: Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci 2009;12:1567-1576.
27.
Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, Nicoll RA, Edwards RH: Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 2010;65:66-79.
28.
Yasuda T, Nakata Y, Choong CJ, Mochizuki H: Neurodegenerative changes initiated by presynaptic dysfunction. Transl Neurodegener 2013;2:16.
29.
Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R: Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 1991;30:572-580.
30.
Jeffrey M, Halliday WG, Bell J, Johnston AR, MacLeod NK, Ingham C, Sayers AR, Brown DA, Fraser JR: Synapse loss associated with abnormal PrP precedes neuronal degeneration in the scrapie-infected murine hippocampus. Neuropathol Appl Neurobiol 2000;26:41-54.
31.
Behl C: Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. Prog Neurobiol 1999;57:301-323.
32.
Ebadi M, Srinivasan SK, Baxi MD: Oxidative stress and antioxidant therapy in Parkinson's disease. Prog Neurobiol 1996;48:1-19.
33.
Brown DR, Wong BS, Hafiz F, Clive C, Haswell SJ, Jones IM: Normal prion protein has an activity like that of superoxide dismutase. Biochem J 1999;344:1-5.
34.
Milhavet O, McMahon HE, Rachidi W, Nishida N, Katamine S, Mange A, Arlotto M, Casanova D, Riondel J, Favier A, Lehmann S: Prion infection impairs the cellular response to oxidative stress. Proc Natl Acad Sci U S A 2000;97:13937-13942.
35.
Brown DR, Nicholas RS, Canevari L: Lack of prion protein expression results in a neuronal phenotype sensitive to stress. J Neurosci Res 2002;67:211-224.
36.
Grant WB: Dietary links to Alzheimer's disease: 1999 update. J Alzheimers Dis 1999;1:197-201.
37.
Zhang P, Liu B, Kang SW, Seo MS, Rhee SG, Obeid LM: Thioredoxin peroxidase is a novel inhibitor of apoptosis with a mechanism distinct from that of Bcl-2. J Biol Chem 1997;272:30615-30618.
38.
Nonn L, Berggren M, Powis G: Increased expression of mitochondrial peroxiredoxin-3 (thioredoxin peroxidase-2) protects cancer cells against hypoxia and drug-induced hydrogen peroxide-dependent apoptosis. Mol Cancer Res 2003;1:682-689.
39.
Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE: Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 2005;57:695-703.
40.
Blass JP, Gibson GE: Cerebrometabolic aspects of delirium in relationship to dementia. Dement Geriatr Cogn Disord 1999;10:335-338.
41.
Strom A, Wang GS, Scott FW: Impaired glucose tolerance in mice lacking cellular prion protein. Pancreas 2011;40:229-232.
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