Changes in Synaptic Proteins Precede Neurodegeneration Markers in Preclinical Alzheimer's Disease Cerebrospinal Fluid.
Aged
Alzheimer Disease
/ cerebrospinal fluid
Autopsy
Biomarkers
/ cerebrospinal fluid
Calcium-Binding Proteins
/ cerebrospinal fluid
Early Diagnosis
Female
Humans
Male
Nerve Tissue Proteins
/ cerebrospinal fluid
Prodromal Symptoms
Prognosis
Proteomics
/ methods
Receptors, AMPA
/ metabolism
Synapses
/ metabolism
Syntaxin 1
/ cerebrospinal fluid
Thy-1 Antigens
/ cerebrospinal fluid
Alzheimer's disease
Biomarker: Prognostic
Cerebrospinal fluid
Clinical proteomics
Selected reaction monitoring
Journal
Molecular & cellular proteomics : MCP
ISSN: 1535-9484
Titre abrégé: Mol Cell Proteomics
Pays: United States
ID NLM: 101125647
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
20
12
2018
pubmed:
5
1
2019
medline:
26
11
2019
entrez:
5
1
2019
Statut:
ppublish
Résumé
A biomarker of synapse loss, an early event in Alzheimer's disease (AD) pathophysiology that precedes neuronal death and symptom onset, would be a much-needed prognostic biomarker. With direct access to the brain interstitial fluid, the cerebrospinal fluid (CSF) is a potential source of synapse-derived proteins. In this study, we aimed to identify and validate novel CSF biomarkers of synapse loss in AD. Discovery: Combining shotgun proteomics of the CSF with an exhaustive search of the literature and public databases, we identified 251 synaptic proteins, from which we selected 22 for further study. Verification: Twelve proteins were discarded because of poor detection by Selected Reaction Monitoring (SRM). We confirmed the specific expression of 9 of the remaining proteins (Calsynytenin-1, GluR2, GluR4, Neurexin-2A, Neurexin-3A, Neuroligin-2, Syntaxin-1B, Thy-1, Vamp-2) at the human synapse using Array Tomography microscopy and biochemical fractionation methods. Exploration: Using SRM, we monitored these 9 synaptic proteins (20 peptides) in a cohort of CSF from cognitively normal controls and subjects in the pre-clinical and clinical AD stages (
Identifiants
pubmed: 30606734
pii: S1535-9476(20)31857-0
doi: 10.1074/mcp.RA118.001290
pmc: PMC6398205
doi:
Substances chimiques
Biomarkers
0
CLSTN1 protein, human
0
Calcium-Binding Proteins
0
Nerve Tissue Proteins
0
Receptors, AMPA
0
STX1B protein, human
0
Syntaxin 1
0
Thy-1 Antigens
0
glutamate receptor ionotropic, AMPA 4
0
neurexin IIIalpha
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
546-560Informations de copyright
© 2019 Lleó et al.
Références
J Proteome Res. 2005 May-Jun;4(3):725-33
pubmed: 15952719
Mol Neurobiol. 2005 Dec;32(3):237-49
pubmed: 16385140
Biol Open. 2012 Aug 15;1(8):761-74
pubmed: 23213470
Mult Scler Int. 2011;2011:246412
pubmed: 22096631
J Neurosci. 2014 Jan 15;34(3):804-16
pubmed: 24431439
J Biol Chem. 2004 Jan 9;279(2):987-1002
pubmed: 14532281
Mol Cell Proteomics. 2010 Sep;9(9):2063-75
pubmed: 20811074
Alzheimers Res Ther. 2018 Jan 15;10(1):5
pubmed: 29370833
Nucleic Acids Res. 2016 Jan 4;44(D1):D447-56
pubmed: 26527722
J Biol Chem. 2013 Nov 29;288(48):34906-19
pubmed: 24136198
Alzheimers Dement. 2015 Oct;11(10):1180-90
pubmed: 25533203
Proteomics. 2009 Jun;9(12):3303-15
pubmed: 19562802
Mol Neurodegener. 2015 Apr 09;10:18
pubmed: 25881291
PLoS Biol. 2015 Oct 05;13(10):e1002267
pubmed: 26437117
Science. 2002 Oct 25;298(5594):789-91
pubmed: 12399581
Neurobiol Aging. 2013 Jun;34(6):1653-61
pubmed: 23273601
Neuron. 2015 Jan 7;85(1):173-189
pubmed: 25569349
PLoS One. 2015 Sep 25;10(9):e0138950
pubmed: 26407320
Alzheimers Res Ther. 2016 Oct 3;8(1):41
pubmed: 27716408
Science. 1992 Jul 10;257(5067):255-9
pubmed: 1321498
Nat Genet. 2014 Dec;46(12):1327-32
pubmed: 25362483
Brain Struct Funct. 2017 Dec;222(9):4149-4161
pubmed: 28643105
Neurobiol Aging. 2005 Feb;26(2):207-27
pubmed: 15582749
Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1038-43
pubmed: 18195348
J Comp Neurol. 1999 Jul 26;410(2):256-64
pubmed: 10414531
Alzheimers Dement. 2011 May;7(3):270-9
pubmed: 21514249
Cell. 2013 Jul 3;154(1):75-88
pubmed: 23827676
Bioinformatics. 2014 Sep 1;30(17):2524-6
pubmed: 24794931
J Neurosci. 2014 Jun 25;34(26):8716-27
pubmed: 24966372
Science. 2014 May 30;344(6187):1023-8
pubmed: 24876496
J Proteome Res. 2006 Oct;5(10):2769-79
pubmed: 17022648
Mol Cell Neurosci. 2001 Jan;17(1):226-40
pubmed: 11161481
Brain. 2017 Dec 1;140(12):3204-3214
pubmed: 29177427
J Neurochem. 2005 Mar;92(6):1306-16
pubmed: 15748150
Proteomics. 2004 Oct;4(10):3141-55
pubmed: 15378707
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11999-2004
pubmed: 20547835
Mol Cell Proteomics. 2006 Jun;5(6):1158-70
pubmed: 16507876
J Neurochem. 2014 Nov;131(3):268-83
pubmed: 25040546
PLoS One. 2010 Jun 11;5(6):e10980
pubmed: 20552007
J Neuropathol Exp Neurol. 1992 Mar;51(2):133-41
pubmed: 1347079
J Neurosci. 2014 Feb 12;34(7):2702-12
pubmed: 24523559
PLoS One. 2012;7(8):e42555
pubmed: 22880031
Neuropharmacology. 2014 Apr;79:172-9
pubmed: 24445080
Nat Neurosci. 2011 Jan;14(1):19-21
pubmed: 21170055
Cell. 2004 Dec 29;119(7):1013-26
pubmed: 15620359
Neuron. 2014 May 21;82(4):756-71
pubmed: 24853936
Alzheimers Dement. 2013 May;9(3):251-61
pubmed: 23622690
Proc Natl Acad Sci U S A. 2004 Mar 16;101(11):3833-8
pubmed: 15007177
Brain Res. 2010 Nov 29;1362:13-22
pubmed: 20875798
J Neurosci. 2014 May 21;34(21):7266-80
pubmed: 24849359
PLoS One. 2012;7(10):e46683
pubmed: 23071613
Neurology. 2015 Aug 18;85(7):626-33
pubmed: 26180139
Mol Neurodegener. 2014 Nov 23;9:53
pubmed: 25418885
Neuron. 2013 Apr 24;78(2):285-97
pubmed: 23622064
Synapse. 2017 Jun;71(6):
pubmed: 28196395
Neuroscience. 2004;128(2):219-28
pubmed: 15350635
Eur J Neurosci. 1996 Oct;8(10):2068-74
pubmed: 8921297
Mol Syst Biol. 2009;5:269
pubmed: 19455133
Nature. 2004 Feb 26;427(6977):801
pubmed: 14985749
J Cell Biol. 1998 Feb 9;140(3):685-98
pubmed: 9456327
J Neurochem. 2009 Feb;108(3):662-75
pubmed: 19187093
Am J Hum Genet. 2012 Jan 13;90(1):133-41
pubmed: 22209245
Pain. 2016 Jun;157(6):1314-24
pubmed: 26859820
J Neurosci. 2009 May 20;29(20):6479-89
pubmed: 19458219
PLoS One. 2009;4(4):e5230
pubmed: 19381277
PLoS One. 2015 Oct 21;10(10):e0140868
pubmed: 26488171
J Neurosci. 2000 Jun 1;20(11):4069-80
pubmed: 10818142
J Proteome Res. 2004 Jan-Feb;3(1):97-103
pubmed: 14998169
Mol Cell Proteomics. 2014 Nov;13(11):3152-63
pubmed: 25038066
Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1469-73
pubmed: 8641850
J Alzheimers Dis. 2010;21(2):655-66
pubmed: 20571220
Nat Neurosci. 2014 Jan;17(1):56-64
pubmed: 24336150
Neuropathol Appl Neurobiol. 2016 Feb;42(1):77-94
pubmed: 26613567
Mol Cell Neurosci. 2001 Jan;17(1):151-66
pubmed: 11161476
Mol Cell Neurosci. 2005 Jan;28(1):128-40
pubmed: 15607948
J Biol Chem. 2000 Dec 22;275(51):39803-6
pubmed: 11036064
Cell. 2006 Nov 17;127(4):831-46
pubmed: 17110340
J Biol Chem. 2004 May 14;279(20):21003-11
pubmed: 15020595
Clin Proteomics. 2016 May 15;13:11
pubmed: 27186164
Int Rev Neurobiol. 2006;73:29-98
pubmed: 16737901
Expert Opin Ther Targets. 2016 Oct;20(10):1195-207
pubmed: 27167520
J Neurosci Res. 1999 Aug 1;57(3):315-23
pubmed: 10412022
Hum Mol Genet. 2011 Aug 1;20(15):3042-51
pubmed: 21551456
Exp Mol Med. 2013 Sep 06;45:e39
pubmed: 24008896
J Biol Chem. 2017 May 5;292(18):7327-7337
pubmed: 28283575
J Neurochem. 2006 Apr;97 Suppl 1:16-23
pubmed: 16635246
Cell. 2000 Jun 9;101(6):657-69
pubmed: 10892652
Hum Mol Genet. 2012 Jul 1;21(13):2845-54
pubmed: 22434822
Alzheimers Dement. 2011 May;7(3):263-9
pubmed: 21514250
J Proteomics. 2015 Apr 24;119:90-9
pubmed: 25661039
Mol Brain. 2014 Nov 28;7:88
pubmed: 25429717
J Proteome Res. 2005 Mar-Apr;4(2):306-15
pubmed: 15822905
J Neurochem. 2005 Dec;95(6):1732-45
pubmed: 16269012
Mol Cell Neurosci. 2014 Mar;59:106-18
pubmed: 24534009
J Alzheimers Dis. 2017;58(3):909-918
pubmed: 28527215
Alzheimers Dement. 2011 May;7(3):280-92
pubmed: 21514248
Neurobiol Aging. 2014 Apr;35(4):746-56
pubmed: 24211009
Nature. 1996 Feb 29;379(6568):826-9
pubmed: 8587606