Abstract
Alzheimer's disease (AD) is progressive brain amyloidosis that damages brain regions associated with memory, thinking, behavioral and social skills. Neuropathologically, AD is characterized by intraneuronal hyperphosphorylated tau inclusions as neurofibrillary tangles (NFTs), and buildup of extracellular amyloid-beta (Aβ) peptide as senile plaques. Several biomarker tests capturing these pathologies have been developed. However, for the full clinical expression of the neurodegenerative events of AD, there exist other central molecular pathways. In terms of understanding the unidentified underlying processes for the progression and development of AD, a complete comprehension of the structure and composition of atypical aggregation of proteins is essential. Presently, to aid the prognosis, diagnosis, detection, and development of drug targets in AD, neuroproteomics is elected as one of the leading essential tools for the efficient exploratory discovery of prospective biomarker candidates estimated to play a crucial role. Therefore, the aim of this review is to present the role of neuroproteomics to analyze the complexity of AD.
Keywords: Neuroproteomics, Alzheimer's Disease, Amyloid precursor protein, Amyloid-beta, Tau, Microglia, Biomarkers.
Graphical Abstract
[http://dx.doi.org/10.2174/1386207323666200117103144 ] [PMID: 31957612]
[http://dx.doi.org/10.1007/s12035-019-01660-3 ] [PMID: 31209782]
[http://dx.doi.org/10.1016/j.scitotenv.2020.138313]
[http://dx.doi.org/10.1016/j.jalz.2016.07.150 ] [PMID: 27583652]
[http://dx.doi.org/10.1159/000449482 ] [PMID: 27780989]
[http://dx.doi.org/10.1155/2020/5086250] [PMID: 32509144]
[http://dx.doi.org/10.1146/annurev-med-042915-103753 ] [PMID: 28099083]
[http://dx.doi.org/10.1016/j.lfs.2019.03.055 ] [PMID: 30914316]
[http://dx.doi.org/10.1155/2013/254954] [PMID: 23984328]
[http://dx.doi.org/10.2174/1381612825666191008103141 ] [PMID: 31593530]
[http://dx.doi.org/10.1007/s40142-018-0155-8]
[http://dx.doi.org/10.1038/ng.3246 ] [PMID: 25807283]
[http://dx.doi.org/10.1038/ng.3916 ] [PMID: 28714976]
[http://dx.doi.org/10.1038/nm.3736 ] [PMID: 25419706]
[http://dx.doi.org/10.1038/nrn.2016.7 ] [PMID: 26911435]
[http://dx.doi.org/10.1101/cshperspect.a006296 ] [PMID: 23028126]
[http://dx.doi.org/10.3389/fncel.2015.00124 ] [PMID: 25914621]
[http://dx.doi.org/10.1016/j.neuron.2018.06.030 ] [PMID: 30001512]
[http://dx.doi.org/10.1016/j.neuron.2018.05.023 ] [PMID: 29937276]
[http://dx.doi.org/10.1016/j.jalz.2011.10.007 ] [PMID: 22265587]
[http://dx.doi.org/10.1007/s12035-018-1420-2 ] [PMID: 30414087]
[http://dx.doi.org/10.1038/nrn2194 ] [PMID: 17684513]
[http://dx.doi.org/10.4103/1673-5374.274329 ] [PMID: 31997800]
[http://dx.doi.org/10.3389/fcell.2019.00197 ] [PMID: 31620438]
[http://dx.doi.org/10.1159/000481812 ] [PMID: 29887680]
[http://dx.doi.org/10.1111/psyg.12368 ] [PMID: 30221441]
[http://dx.doi.org/10.1016/j.bbrc.2019.05.131 ] [PMID: 31164199]
[http://dx.doi.org/10.1016/j.neuron.2010.04.031 ] [PMID: 20547123]
[http://dx.doi.org/10.1101/cshperspect.a006320 ] [PMID: 23002015]
[http://dx.doi.org/10.1016/j.trci.2018.03.009 ] [PMID: 29955663]
[http://dx.doi.org/10.3390/medsci6020045 ] [PMID: 29865246]
[http://dx.doi.org/10.1056/NEJMoa1705971 ] [PMID: 29365294]
[http://dx.doi.org/10.2174/156720511795745348 ] [PMID: 21222594]
[http://dx.doi.org/10.1016/j.cell.2015.12.056 ] [PMID: 26871627]
[http://dx.doi.org/10.2174/1381612825666191011102444 ] [PMID: 31604413]
[http://dx.doi.org/10.1002/ana.22615 ] [PMID: 22028219]
[http://dx.doi.org/10.1016/j.scitotenv.2019.134836 ] [PMID: 31704512]
[http://dx.doi.org/10.1016/j.bbadis.2014.04.012 ] [PMID: 24747741]
[http://dx.doi.org/10.1002/gps.724 ] [PMID: 12325056]
[http://dx.doi.org/10.1146/annurev-pharmtox-011613-135928 ] [PMID: 24160693]
[http://dx.doi.org/10.1016/j.jalz.2012.05.2116 ] [PMID: 22748938]
[http://dx.doi.org/10.2174/1381612826666200107142541 ] [PMID: 31914904]
[http://dx.doi.org/10.4018/978-1-7998-1317-0]
[http://dx.doi.org/10.1146/annurev-biochem-072909-100424 ] [PMID: 22439968]
[http://dx.doi.org/10.1016/j.copbio.2011.11.014 ] [PMID: 22169889]
[http://dx.doi.org/10.1016/j.tins.2008.10.003 ] [PMID: 19135729]
[http://dx.doi.org/10.1016/j.bbapap.2015.01.016 ] [PMID: 25680928]
[http://dx.doi.org/10.1023/B:NERE.0000023618.35579.7c ] [PMID: 15176488]
[http://dx.doi.org/10.3233/JAD-143006 ] [PMID: 26401553]
[http://dx.doi.org/10.1016/j.bcp.2013.11.009 ] [PMID: 24275164]
[http://dx.doi.org/10.1016/j.neurol.2013.07.016 ] [PMID: 24041475]
[http://dx.doi.org/10.1007/s12603-013-0003-1 ] [PMID: 23299381]
[http://dx.doi.org/10.1016/j.mcna.2012.12.013 ] [PMID: 23642578]
[http://dx.doi.org/10.3233/JAD-2012-129030 ] [PMID: 22735677]
[http://dx.doi.org/10.1038/nrneurol.2012.202 ] [PMID: 23007701]
[http://dx.doi.org/10.1016/j.pneurobio.2011.09.011 ] [PMID: 22005514]
[http://dx.doi.org/10.1586/erm.10.48 ] [PMID: 20629514]
[http://dx.doi.org/10.1186/1750-1326-8-20 ] [PMID: 23800368]
[http://dx.doi.org/10.1101/cshperspect.a006221 ] [PMID: 22951438]
[http://dx.doi.org/10.1016/j.jalz.2013.01.013 ] [PMID: 23850333]
[http://dx.doi.org/10.1016/j.jalz.2014.08.099 ] [PMID: 25282381]
[http://dx.doi.org/10.1016/j.jalz.2013.10.007 ] [PMID: 24365657]
[http://dx.doi.org/10.1186/alzrt185 ] [PMID: 23795953]
[http://dx.doi.org/10.1016/j.pneurobio.2012.06.007 ] [PMID: 22743552]
[http://dx.doi.org/10.1016/j.jalz.2014.02.004 ] [PMID: 24795085]
[http://dx.doi.org/10.1038/nrneurol.2010.4 ] [PMID: 20157306]
[http://dx.doi.org/10.1016/j.expneurol.2009.09.024 ] [PMID: 19815015]
[http://dx.doi.org/10.1016/j.exger.2009.10.010 ] [PMID: 19853650]
[http://dx.doi.org/10.3233/JAD-140852 ] [PMID: 24916542]
[http://dx.doi.org/10.1016/j.jalz.2013.04.506 ] [PMID: 23850330]
[http://dx.doi.org/10.2217/bmm.11.50 ] [PMID: 21861661]
[http://dx.doi.org/10.1016/j.pneurobio.2011.09.004 ] [PMID: 21945642]
[http://dx.doi.org/10.1038/nrd3115 ] [PMID: 20592748]
[http://dx.doi.org/10.3233/JAD-2006-9S317 ] [PMID: 16914853]
[http://dx.doi.org/10.1074/jbc.M300825200 ] [PMID: 12840029]
[http://dx.doi.org/10.1080/13506120500106958 ] [PMID: 16011984]
[http://dx.doi.org/10.1016/j.jns.2020.116974]]
[http://dx.doi.org/10.1056/NEJMoa1304839 ] [PMID: 24450891]
[http://dx.doi.org/10.2174/1568026620666200422105156] [PMID: 32321405]
[http://dx.doi.org/10.1056/NEJMe1313943 ] [PMID: 24450897]
[http://dx.doi.org/10.1016/j.bbapap.2015.01.009 ] [PMID: 25619854]
[http://dx.doi.org/10.2174/156720508786898488 ] [PMID: 19075583]
[http://dx.doi.org/10.1016/j.neurobiolaging.2004.11.010 ] [PMID: 16298240]
[http://dx.doi.org/10.1007/978-3-7091-6262-0_23]
[http://dx.doi.org/10.1023/A:1020941929414 ] [PMID: 12462422]
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.05.005 ] [PMID: 15950321]
[http://dx.doi.org/10.1002/1615-9861(200111)1:12<1519:AID-PROT1519>3.0.CO;2-L ] [PMID: 11747211]
[http://dx.doi.org/10.3233/JAD-2007-11203 ] [PMID: 17522440]
[http://dx.doi.org/10.1074/jbc.M502255200 ] [PMID: 15799962]
[http://dx.doi.org/10.1074/jbc.M314124200 ] [PMID: 14722078]
[http://dx.doi.org/10.3233/JAD-2004-6306 ] [PMID: 15201480]
[http://dx.doi.org/10.1002/(SICI)1522-2683(19990101)20:4/5<928:AID-ELPS928>3.0.CO;2-Z ] [PMID: 10344268]
[http://dx.doi.org/10.1016/j.nbd.2005.05.021 ] [PMID: 15979880]
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.09.021 ] [PMID: 16271804]
[http://dx.doi.org/10.1016/j.nbd.2005.10.004 ] [PMID: 16378731]
[http://dx.doi.org/10.1002/prca.200800161 ] [PMID: 20333275]
[http://dx.doi.org/10.1016/j.jchromb.2013.05.003 ] [PMID: 23735279]
[http://dx.doi.org/10.1021/pr501076j ] [PMID: 25490617]
[http://dx.doi.org/10.1002/rcm.7777 ] [PMID: 27813239]
[http://dx.doi.org/10.1002/prca.201600009 ] [PMID: 27863112]
[http://dx.doi.org/10.1186/1750-1326-9-22 ] [PMID: 24902845]
[http://dx.doi.org/10.1074/mcp.M114.040576 ] [PMID: 25556233]
[http://dx.doi.org/10.1371/journal.pone.0135365 ] [PMID: 26270474]
[http://dx.doi.org/10.1186/s13024-015-0059-y ] [PMID: 26627638]
[http://dx.doi.org/10.1038/tp.2016.194 ] [PMID: 27845782]
[http://dx.doi.org/10.1179/016164106X98035 ] [PMID: 16551433]
[http://dx.doi.org/10.1097/00001756-200204160-00015 ] [PMID: 11973456]
[http://dx.doi.org/10.1016/j.molbrainres.2003.08.005 ] [PMID: 14559363]
[http://dx.doi.org/10.1016/j.jprot.2018.04.027 ] [PMID: 29684683]
[http://dx.doi.org/10.1002/prca.201700131 ] [PMID: 29028155]
[http://dx.doi.org/10.1002/prca.201400178 ] [PMID: 25676562]
[http://dx.doi.org/10.1373/clinchem.2006.078014 ] [PMID: 17289803]
[http://dx.doi.org/10.1021/pr5006058 ] [PMID: 25091646]
[http://dx.doi.org/10.1002/prca.201700100 ] [PMID: 28972305]
[http://dx.doi.org/10.1038/269604a0 ] [PMID: 199847]
[PMID: 7263700]
[PMID: 7068630]
[http://dx.doi.org/10.1038/nrneurol.2012.263 ] [PMID: 23296339]
[http://dx.doi.org/10.1007/s00401-014-1266-2 ] [PMID: 24633805]
[http://dx.doi.org/10.1093/hmg/dds296 ] [PMID: 22821396]
[http://dx.doi.org/10.1371/journal.pone.0042555 ] [PMID: 22880031]
[http://dx.doi.org/10.1016/j.brainres.2013.03.019 ] [PMID: 23541617]
[http://dx.doi.org/10.1111/febs.12590 ] [PMID: 24279329]
[http://dx.doi.org/10.1073/pnas.1102664108 ] [PMID: 21712440]
[http://dx.doi.org/10.1002/jms.2987 ] [PMID: 22576872]
[http://dx.doi.org/10.1021/pr800758g ] [PMID: 19093876]
[http://dx.doi.org/10.1016/j.expneurol.2009.06.011 ] [PMID: 19559702]
[http://dx.doi.org/10.1021/ac3033239 ] [PMID: 23186391]
[http://dx.doi.org/10.2217/17520363.1.1.59 ] [PMID: 20477461]
[http://dx.doi.org/10.2174/1381612826666200406075044 ] [PMID: 32250219]
[http://dx.doi.org/10.3390/molecules25061267 ] [PMID: 32168835]
[http://dx.doi.org/10.1186/alzrt82 ] [PMID: 21639952]
[http://dx.doi.org/10.1074/jbc.R800010200 ] [PMID: 18650432]
[http://dx.doi.org/10.1111/jphp.13244] [PMID: 32149402]
[http://dx.doi.org/10.1016/j.neurobiolaging.2009.06.002 ] [PMID: 19604603]
[http://dx.doi.org/10.1016/S0006-291X(84)80190-4 ] [PMID: 6375662]
[http://dx.doi.org/10.1073/pnas.82.12.4245 ] [PMID: 3159021]
[http://dx.doi.org/10.1038/359325a0 ] [PMID: 1406936]
[http://dx.doi.org/10.1016/j.jalz.2011.03.008 ] [PMID: 21514249]
[http://dx.doi.org/10.1111/j.1471-4159.2011.07510.x ] [PMID: 22122230]
[http://dx.doi.org/10.2174/138161211797416039 ] [PMID: 21728980]
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb09841.x ] [PMID: 8229004]
[http://dx.doi.org/10.1001/archneurol.2012.2194 ] [PMID: 22892585]
[http://dx.doi.org/10.1186/alzrt30 ] [PMID: 20350302]
[http://dx.doi.org/10.3233/JAD-2012-121471 ] [PMID: 23076076]
[http://dx.doi.org/10.1016/j.ab.2011.08.010 ] [PMID: 21888888]
[http://dx.doi.org/10.3233/JAD-132489 ] [PMID: 24625802]
[http://dx.doi.org/10.1373/clinchem.2013.220392 ] [PMID: 24842955]
[http://dx.doi.org/10.1016/j.arr.2020.101046 ] [PMID: 32171783]
[http://dx.doi.org/10.1007/s12035-020-01911-8 ] [PMID: 32297302]
[http://dx.doi.org/10.1073/pnas.83.13.4913 ] [PMID: 3088567]
[http://dx.doi.org/10.1016/S0304-3940(00)01036-3 ] [PMID: 10788705]
[http://dx.doi.org/10.1021/pr7008669 ] [PMID: 18351740]
[http://dx.doi.org/10.1373/clinchem.2013.216515 ] [PMID: 24566260]
[http://dx.doi.org/10.1016/j.febslet.2006.05.029 ] [PMID: 16753151]
[http://dx.doi.org/10.1111/j.1460-9568.2008.06329.x ] [PMID: 18702695]
[http://dx.doi.org/10.1016/j.brainres.2006.10.085 ] [PMID: 17169350]
[http://dx.doi.org/10.1111/j.1460-9568.2006.04986.x ] [PMID: 16930434]
[PMID: 2602435]
[http://dx.doi.org/10.1016/S0022-1759(02)00006-6 ] [PMID: 11983234]
[http://dx.doi.org/10.1016/j.febslet.2004.04.098 ] [PMID: 15196943]
[http://dx.doi.org/10.1073/pnas.85.13.4884 ] [PMID: 2455299]
[http://dx.doi.org/10.1073/pnas.85.12.4506 ] [PMID: 3132715]
[http://dx.doi.org/10.1016/j.febslet.2007.11.067 ] [PMID: 18061582]
[http://dx.doi.org/10.1016/j.intimp.2020.106479 ] [PMID: 32353686]
[http://dx.doi.org/10.1056/NEJMoa1211103 ] [PMID: 23150908]
[http://dx.doi.org/10.1056/NEJMoa1211851 ] [PMID: 23150934]
[http://dx.doi.org/10.1007/s12017-011-8147-9 ] [PMID: 21567187]
[http://dx.doi.org/10.3233/JAD-2012-120787 ] [PMID: 22890100]
[http://dx.doi.org/10.1186/1559-0275-10-19 ] [PMID: 24295388]
[http://dx.doi.org/10.1038/nature01511 ] [PMID: 12634793]
[http://dx.doi.org/10.1074/mcp.M200025-MCP200 ] [PMID: 12118079]
[http://dx.doi.org/10.1007/s00216-012-5918-6 ] [PMID: 22451173]
[http://dx.doi.org/10.2217/bmm.12.39 ] [PMID: 22917143]
[http://dx.doi.org/10.1016/j.molcel.2013.01.029 ] [PMID: 23438854]
[http://dx.doi.org/10.1074/mcp.R200007-MCP200 ] [PMID: 12488461]
[http://dx.doi.org/10.1038/nbt1315 ] [PMID: 17557102]