Review Special Issues

Towards defining the Mechanisms of Alzheimer’s disease based on a contextual analysis of molecular pathways

  • Received: 15 January 2016 Accepted: 17 March 2016 Published: 21 March 2016
  • Alzheimer’s disease (AD) is posing an increasingly profound problem to society. Our genuine understanding of the pathogenesis of AD is inadequate and as a consequence, diagnostic and therapeutic strategies are currently insufficient. The understandable focus of many studies is the identification of molecules with high diagnostic utility however the opportunity to obtain a further understanding of the mechanistic origins of the disease from such putative biomarkers is often overlooked. This study examines the involvement of biomarkers in AD to shed light on potential mechanisms and pathways through which they are implicated in the pathology of this devastating neurodegenerative disorder. The computational tools required to analyse ever-growing datasets in the context of AD are also discussed.

    Citation: Joanna L. Richens, Jonathan P. Bramble, Hannah L. Spencer, Fiona Cantlay, Molly Butler, Paul O’Shea. Towards defining the Mechanisms of Alzheimer’s disease based on a contextual analysis of molecular pathways[J]. AIMS Genetics, 2016, 3(1): 25-48. doi: 10.3934/genet.2016.1.25

    Related Papers:

  • Alzheimer’s disease (AD) is posing an increasingly profound problem to society. Our genuine understanding of the pathogenesis of AD is inadequate and as a consequence, diagnostic and therapeutic strategies are currently insufficient. The understandable focus of many studies is the identification of molecules with high diagnostic utility however the opportunity to obtain a further understanding of the mechanistic origins of the disease from such putative biomarkers is often overlooked. This study examines the involvement of biomarkers in AD to shed light on potential mechanisms and pathways through which they are implicated in the pathology of this devastating neurodegenerative disorder. The computational tools required to analyse ever-growing datasets in the context of AD are also discussed.


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    [1] Strimbu K, Tavel JA (2010) What are Biomarkers? Curr Opin HIV AIDS 5: 463-466. doi: 10.1097/COH.0b013e32833ed177
    [2] Robinson DH, Toledo AH (2012) Historical development of modern anesthesia. J Invest Surg 25: 141-149. doi: 10.3109/08941939.2012.690328
    [3] Pitt D, Aubin JM (2012) Joseph Lister: father of modern surgery. Can J Surg 55: E8-9.
    [4] Hsu JL (2013) A brief history of vaccines: smallpox to the present. S D Med Spec no: 33-37.
    [5] Blevins SM, Bronze MS (2010) Robert Koch and the 'golden age' of bacteriology. Int J Infect Dis 14: e744-751. doi: 10.1016/j.ijid.2009.12.003
    [6] Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69: 89-95. doi: 10.1067/mcp.2001.113989
    [7] O'Donnell MJ, Xavier D, Liu L, et al. (2010) Risk factors for ischaemic and intracerebral haemorrhagic stroke in 22 countries (the INTERSTROKE study): a case-control study. Lancet 376: 112-123. doi: 10.1016/S0140-6736(10)60834-3
    [8] Richens JL, Urbanowicz RA, Lunt EA, et al. (2009) Systems biology coupled with label-free high-throughput detection as a novel approach for diagnosis of chronic obstructive pulmonary disease. Respir Res 10: 29. doi: 10.1186/1465-9921-10-29
    [9] Song IU, Chung YA, Chung SW, et al. (2014) Early diagnosis of Alzheimer's disease and Parkinson's disease associated with dementia using cerebral perfusion SPECT. Dement Geriatr Cogn Disord 37: 276-285. doi: 10.1159/000357128
    [10] Perazella MA (2015) The Urine Sediment as a Biomarker of Kidney Disease. Am J Kidney Dis 66: 748-755. doi: 10.1053/j.ajkd.2015.02.342
    [11] Felton HT, Derrick JB, Swartz DP (1964) A Simple Immunologic Test For Pregnancy. Can Med Assoc J 91: 996-1000.
    [12] Slamon DJ, Clark GM, Wong SG, et al. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177-182. doi: 10.1126/science.3798106
    [13] Puglisi F, Fontanella C, Amoroso V, et al. (2015) Current challenges in HER2-positive breast cancer. Crit Rev Oncol Hematol 98: 211-221.
    [14] Anderson NL, Ptolemy AS, Rifai N (2013) The riddle of protein diagnostics: future bleak or bright? Clin Chem 59: 194-197. doi: 10.1373/clinchem.2012.184705
    [15] Mayeux R (2004) Biomarkers: potential uses and limitations. NeuroRx 1: 182-188. doi: 10.1602/neurorx.1.2.182
    [16] Anderson NL, Anderson NG (2002) The human plasma proteome: history, character, and diagnostic prospects. Mol Cell Proteomics 1: 845-867. doi: 10.1074/mcp.R200007-MCP200
    [17] Krebs HA (1950) Chemical composition of blood plasma and serum. Annu Rev Biochem 19: 409-430. doi: 10.1146/annurev.bi.19.070150.002205
    [18] Richens JL, Lunt EA, Sanger D, et al. (2009) Avoiding nonspecific interactions in studies of the plasma proteome: practical solutions to prevention of nonspecific interactions for label-free detection of low-abundance plasma proteins. J Proteome Res 8: 5103-5110. doi: 10.1021/pr900487y
    [19] Drucker E, Krapfenbauer K (2013) Pitfalls and limitations in translation from biomarker discovery to clinical utility in predictive and personalised medicine. EPMA J 4: 7. doi: 10.1186/1878-5085-4-7
    [20] Lim LS, Sherin K (2008) Screening for prostate cancer in U.S. men ACPM position statement on preventive practice. Am J Prev Med 34: 164-170. doi: 10.1016/j.amepre.2007.10.003
    [21] Prince M, Bryce R, Albanese E, et al. (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9: 63-75 e62. doi: 10.1016/j.jalz.2012.11.007
    [22] Galvin JE, Sadowsky CH (2012) Practical guidelines for the recognition and diagnosis of dementia. J Am Board Fam Med 25: 367-382. doi: 10.3122/jabfm.2012.03.100181
    [23] Bekris LM, Yu CE, Bird TD, et al. (2010) Genetics of Alzheimer disease. J Geriatr Psychiatry Neurol 23: 213-227. doi: 10.1177/0891988710383571
    [24] Wu L, Rosa-Neto P, Hsiung GY, et al. (2012) Early-onset familial Alzheimer's disease (EOFAD). Can J Neurol Sci 39: 436-445. doi: 10.1017/S0317167100013949
    [25] Ballard C, Gauthier S, Corbett A, et al. (2011) Alzheimer's disease. Lancet 377: 1019-1031. doi: 10.1016/S0140-6736(10)61349-9
    [26] Castello MA, Jeppson JD, Soriano S (2014) Moving beyond anti-amyloid therapy for the prevention and treatment of Alzheimer’s disease. BMC Neurol 14: 1-5. doi: 10.1186/1471-2377-14-1
    [27] Cedazo-Minguez A, Winblad B (2010) Biomarkers for Alzheimer's disease and other forms of dementia: clinical needs, limitations and future aspects. Exp Gerontol 45: 5-14. doi: 10.1016/j.exger.2009.09.008
    [28] Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci 12: 383-388. doi: 10.1016/0165-6147(91)90609-V
    [29] Puzzo D, Gulisano W, Arancio O, et al. (2015) The keystone of Alzheimer pathogenesis might be sought in Abeta physiology. Neuroscience 307: 26-36. doi: 10.1016/j.neuroscience.2015.08.039
    [30] Fiandaca MS, Mapstone ME, Cheema AK, et al. (2014) The critical need for defining preclinical biomarkers in Alzheimer'sdisease. Alzheimers Dement 10: S196-S212. doi: 10.1016/j.jalz.2014.04.015
    [31] Racchi M, Govoni S (2003) The pharmacology of amyloid precursor protein processing. Exp Gerontol 38: 145-157. doi: 10.1016/S0531-5565(02)00158-4
    [32] Nhan HS, Chiang K, Koo EH (2015) The multifaceted nature of amyloid precursor protein and its proteolytic fragments: friends and foes. Acta Neuropathol 129: 1-19. doi: 10.1007/s00401-014-1347-2
    [33] Chasseigneaux S, Allinquant B (2012) Functions of Abeta, sAPPalpha and sAPPbeta : similarities and differences. J Neurochem 120 Suppl 1: 99-108. doi: 10.1111/j.1471-4159.2011.07584.x
    [34] Simic G, Babic Leko M, Wray S, et al. (2016) Tau Protein Hyperphosphorylation and Aggregation in Alzheimer's Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules 6.
    [35] Wang Y, Mandelkow E (2016) Tau in physiology and pathology. Nat Rev Neurosci 17: 22-35.
    [36] Wang JZ, Xia YY, Grundke-Iqbal I, et al. (2013) Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J Alzheimers Dis 33 Suppl 1: S123-139.
    [37] Robakis NK (2010) Are Abeta and its derivatives causative agents or innocent bystanders in AD? Neurodegener Dis 7: 32-37. doi: 10.1159/000266476
    [38] Castello MA, Soriano S (2014) On the origin of Alzheimer's disease. Trials and tribulations of the amyloid hypothesis. Ageing Res Rev 13: 10-12. doi: 10.1016/j.arr.2013.10.001
    [39] Loy CT, Schofield PR, Turner AM, et al. (2014) Genetics of dementia. Lancet 383: 828-840. doi: 10.1016/S0140-6736(13)60630-3
    [40] Arriagada PV, Growdon JH, Hedley-Whyte ET, et al. (1992) Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease. Neurology 42: 631-639. doi: 10.1212/WNL.42.3.631
    [41] Crystal H, Dickson D, Fuld P, et al. (1988) Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 38: 1682-1687. doi: 10.1212/WNL.38.11.1682
    [42] Benilova I, Karran E, De Strooper B (2012) The toxic A[beta] oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci 15: 349-357. doi: 10.1038/nn.3028
    [43] Hardy J (2009) The amyloid hypothesis for Alzheimer's disease: a critical reappraisal. J Neurochem 110: 1129-1134. doi: 10.1111/j.1471-4159.2009.06181.x
    [44] Hsia AY, Masliah E, McConlogue L, et al. (1999) Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci U S A 96: 3228-3233. doi: 10.1073/pnas.96.6.3228
    [45] Mucke L, Masliah E, Yu GQ, et al. (2000) High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 20: 4050-4058.
    [46] Holmes C, Boche D, Wilkinson D, et al. (2008) Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372: 216-223. doi: 10.1016/S0140-6736(08)61075-2
    [47] Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10: 698-712. doi: 10.1038/nrd3505
    [48] Robakis NK (2011) Mechanisms of AD neurodegeneration may be independent of Abeta and its derivatives. Neurobiol Aging 32: 372-379. doi: 10.1016/j.neurobiolaging.2010.05.022
    [49] Richens JL, Morgan K, O'Shea P (2014) Reverse engineering of Alzheimer's disease based on biomarker pathways analysis. Neurobiol Aging 35: 2029-2038. doi: 10.1016/j.neurobiolaging.2014.02.024
    [50] Morgan K (2011) The three new pathways leading to Alzheimer's disease. Neuropathol Appl Neurobiol 37: 353-357. doi: 10.1111/j.1365-2990.2011.01181.x
    [51] Baumgart M, Snyder HM, Carrillo MC, et al. (2015) Summary of the evidence on modifiable risk factors for cognitive decline and dementia: A population-based perspective. Alzheimers Dement 11: 718-726. doi: 10.1016/j.jalz.2015.05.016
    [52] Hebert LE, Scherr PA, Bienias JL, et al. (2003) Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 60: 1119-1122. doi: 10.1001/archneur.60.8.1119
    [53] Moser VA, Pike CJ (2015) Obesity and sex interact in the regulation of Alzheimer's disease. Neurosci Biobehav Rev in press.
    [54] Li R, Singh M (2014) Sex differences in cognitive impairment and Alzheimer's disease. Front Neuroendocrinol 35: 385-403. doi: 10.1016/j.yfrne.2014.01.002
    [55] Barron AM, Pike CJ (2012) Sex hormones, aging, and Alzheimer's disease. Front Biosci (Elite Ed) 4: 976-997.
    [56] Luchsinger JA, Cheng D, Tang MX, et al. (2012) Central obesity in the elderly is related to late-onset Alzheimer disease. Alzheimer Dis Assoc Disord 26: 101-105. doi: 10.1097/WAD.0b013e318222f0d4
    [57] Emmerzaal TL, Kiliaan AJ, Gustafson DR (2015) 2003-2013: a decade of body mass index, Alzheimer's disease, and dementia. J Alzheimers Dis 43: 739-755.
    [58] Tsoi KK, Chan JY, Hirai HW, et al. (2015) Cognitive Tests to Detect Dementia: A Systematic Review and Meta-analysis. JAMA Intern Med 175: 1450-1458. doi: 10.1001/jamainternmed.2015.2152
    [59] Folstein MF, Folstein SE, McHugh PR (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198. doi: 10.1016/0022-3956(75)90026-6
    [60] Mioshi E, Dawson K, Mitchell J, et al. (2006) The Addenbrooke's Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 21: 1078-1085. doi: 10.1002/gps.1610
    [61] Larner AJ, Mitchell AJ (2014) A meta-analysis of the accuracy of the Addenbrooke's Cognitive Examination (ACE) and the Addenbrooke's Cognitive Examination-Revised (ACE-R) in the detection of dementia. Int Psychogeriatr 26: 555-563. doi: 10.1017/S1041610213002329
    [62] Hampel H, Frank R, Broich K, et al. (2010) Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives. Nat Rev Drug Discov 9: 560-574. doi: 10.1038/nrd3115
    [63] Corder EH, Saunders AM, Strittmatter WJ, et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261: 921-923. doi: 10.1126/science.8346443
    [64] Saunders AM, Strittmatter WJ, Schmechel D, et al. (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43: 1467-1472. doi: 10.1212/WNL.43.8.1467
    [65] Xiang Y, Lam SM, Shui G (2015) What can lipidomics tell us about the pathogenesis of Alzheimer disease? Biol Chem 396: 1281-1291.
    [66] Bertram L, McQueen MB, Mullin K, et al. (2007) Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nat Genet 39: 17-23. doi: 10.1038/ng1934
    [67] Corder EH, Saunders AM, Risch NJ, et al. (1994) Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet 7: 180-184. doi: 10.1038/ng0694-180
    [68] Myers RH, Schaefer EJ, Wilson PW, et al. (1996) Apolipoprotein E epsilon4 association with dementia in a population-based study: The Framingham study. Neurology 46: 673-677. doi: 10.1212/WNL.46.3.673
    [69] Barber RC, Phillips NR, Tilson JL, et al. (2015) Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci? PLoS One 10: e0142360. doi: 10.1371/journal.pone.0142360
    [70] Van Cauwenberghe C, Van Broeckhoven C, Sleegers K (2015) The genetic landscape of Alzheimer disease: clinical implications and perspectives. Genet Med in press.
    [71] Karch CM, Goate AM (2015) Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry 77: 43-51. doi: 10.1016/j.biopsych.2014.05.006
    [72] Bertram L, Lill CM, Tanzi RE (2010) The genetics of Alzheimer disease: back to the future. Neuron 68: 270-281. doi: 10.1016/j.neuron.2010.10.013
    [73] Guerreiro R, Wojtas A, Bras J, et al. (2013) TREM2 variants in Alzheimer's disease. N Engl J Med 368: 117-127. doi: 10.1056/NEJMoa1211851
    [74] Harold D, Abraham R, Hollingworth P, et al. (2009) Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat Genet 41: 1088-1093. doi: 10.1038/ng.440
    [75] Hollingworth P, Harold D, Sims R, et al. (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nat Genet 43: 429-435. doi: 10.1038/ng.803
    [76] Lambert JC, Heath S, Even G, et al. (2009) Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease. Nat Genet 41: 1094-1099. doi: 10.1038/ng.439
    [77] Naj AC, Jun G, Beecham GW, et al. (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nat Genet 43: 436-441. doi: 10.1038/ng.801
    [78] Seshadri S, Fitzpatrick AL, Ikram MA, et al. (2010) Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA 303: 1832-1840. doi: 10.1001/jama.2010.574
    [79] Huang Y (2010) Abeta-independent roles of apolipoprotein E4 in the pathogenesis of Alzheimer's disease. Trends Mol Med 16: 287-294. doi: 10.1016/j.molmed.2010.04.004
    [80] Kim J, Yoon H, Basak J, et al. (2014) Apolipoprotein E in synaptic plasticity and Alzheimer's disease: potential cellular and molecular mechanisms. Mol Cells 37: 767-776. doi: 10.14348/molcells.2014.0248
    [81] DeMattos RB, Cirrito JR, Parsadanian M, et al. (2004) ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo. Neuron 41: 193-202. doi: 10.1016/S0896-6273(03)00850-X
    [82] Nathan BP, Bellosta S, Sanan DA, et al. (1994) Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 264: 850-852. doi: 10.1126/science.8171342
    [83] Ji Y, Gong Y, Gan W, et al. (2003) Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients. Neuroscience 122: 305-315. doi: 10.1016/j.neuroscience.2003.08.007
    [84] Lidstrom AM, Bogdanovic N, Hesse C, et al. (1998) Clusterin (apolipoprotein J) protein levels are increased in hippocampus and in frontal cortex in Alzheimer's disease. Exp Neurol 154: 511-521. doi: 10.1006/exnr.1998.6892
    [85] Sihlbom C, Davidsson P, Sjogren M, et al. (2008) Structural and quantitative comparison of cerebrospinal fluid glycoproteins in Alzheimer's disease patients and healthy individuals. Neurochem Res 33: 1332-1340. doi: 10.1007/s11064-008-9588-x
    [86] Nilselid AM, Davidsson P, Nagga K, et al. (2006) Clusterin in cerebrospinal fluid: analysis of carbohydrates and quantification of native and glycosylated forms. Neurochem Int 48: 718-728. doi: 10.1016/j.neuint.2005.12.005
    [87] Jongbloed W, van Dijk KD, Mulder SD, et al. (2015) Clusterin Levels in Plasma Predict Cognitive Decline and Progression to Alzheimer's Disease. J Alzheimers Dis 46: 1103-1110. doi: 10.3233/JAD-150036
    [88] Thambisetty M, Simmons A, Velayudhan L, et al. (2010) Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease. Arch Gen Psychiatry 67: 739-748. doi: 10.1001/archgenpsychiatry.2010.78
    [89] Schrijvers EM, Koudstaal PJ, Hofman A, et al. (2011) Plasma clusterin and the risk of Alzheimer disease. JAMA 305: 1322-1326. doi: 10.1001/jama.2011.381
    [90] McGeer PL, Kawamata T, Walker DG (1992) Distribution of clusterin in Alzheimer brain tissue. Brain Res 579: 337-341. doi: 10.1016/0006-8993(92)90071-G
    [91] Ghiso J, Matsubara E, Koudinov A, et al. (1993) The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex. Biochem J 293 (Pt 1): 27-30.
    [92] Zlokovic BV (1996) Cerebrovascular transport of Alzheimer's amyloid beta and apolipoproteins J and E: possible anti-amyloidogenic role of the blood-brain barrier. Life Sci 59: 1483-1497. doi: 10.1016/0024-3205(96)00310-4
    [93] Giannakopoulos P, Kovari E, French LE, et al. (1998) Possible neuroprotective role of clusterin in Alzheimer's disease: a quantitative immunocytochemical study. Acta Neuropathol 95: 387-394. doi: 10.1007/s004010050815
    [94] Oda T, Wals P, Osterburg HH, et al. (1995) Clusterin (apoJ) alters the aggregation of amyloid beta-peptide (A beta 1-42) and forms slowly sedimenting A beta complexes that cause oxidative stress. Exp Neurol 136: 22-31. doi: 10.1006/exnr.1995.1080
    [95] Li X, Ma Y, Wei X, et al. (2014) Clusterin in Alzheimer's disease: a player in the biological behavior of amyloid-beta. Neurosci Bull 30: 162-168. doi: 10.1007/s12264-013-1391-2
    [96] Jiang T, Tan L, Zhu XC, et al. (2014) Upregulation of TREM2 ameliorates neuropathology and rescues spatial cognitive impairment in a transgenic mouse model of Alzheimer's disease. Neuropsychopharmacology 39: 2949-2962. doi: 10.1038/npp.2014.164
    [97] Zhao Y, Bhattacharjee S, Jones BM, et al. (2013) Regulation of TREM2 expression by an NF-small ka, CyrillicB-sensitive miRNA-34a. Neuroreport 24: 318-323. doi: 10.1097/WNR.0b013e32835fb6b0
    [98] Lue LF, Schmitz C, Walker DG (2015) What happens to microglial TREM2 in Alzheimer's disease: Immunoregulatory turned into immunopathogenic? Neuroscience 302: 138-150. doi: 10.1016/j.neuroscience.2014.09.050
    [99] Jiang T, Yu JT, Zhu XC, et al. (2013) TREM2 in Alzheimer's disease. Mol Neurobiol 48: 180-185. doi: 10.1007/s12035-013-8424-8
    [100] Frank S, Burbach GJ, Bonin M, et al. (2008) TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia 56: 1438-1447. doi: 10.1002/glia.20710
    [101] Paradowska-Gorycka A, Jurkowska M (2013) Structure, expression pattern and biological activity of molecular complex TREM-2/DAP12. Hum Immunol 74: 730-737. doi: 10.1016/j.humimm.2013.02.003
    [102] Paris D, Ait-Ghezala G, Bachmeier C, et al. (2014) The spleen tyrosine kinase (Syk) regulates Alzheimer amyloid-beta production and Tau hyperphosphorylation. J Biol Chem 289: 33927-33944. doi: 10.1074/jbc.M114.608091
    [103] Lebouvier T, Scales TM, Hanger DP, et al. (2008) The microtubule-associated protein tau is phosphorylated by Syk. Biochim Biophys Acta 1783: 188-192. doi: 10.1016/j.bbamcr.2007.11.005
    [104] Vafadar-Isfahani B, Ball G, Coveney C, et al. (2012) Identification of SPARC-like 1 Protein as Part of a Biomarker Panel for Alzheimer's Disease in Cerebrospinal Fluid. J Alzheimers Dis 28: 625-636.
    [105] Richens JL, Vere KA, Light RA, et al. (2014) Practical detection of a definitive biomarker panel for Alzheimer's disease; comparisons between matched plasma and cerebrospinal fluid. Int J Mol Epidemiol Genet 5: 53-70.
    [106] Mendis DB, Ivy GO, Brown IR (2000) Induction of SC1 mRNA encoding a brain extracellular matrix glycoprotein related to SPARC following lesioning of the adult rat forebrain. Neurochem Res 25: 1637-1644. doi: 10.1023/A:1026626805612
    [107] Yin GN, Lee HW, Cho JY, et al. (2009) Neuronal pentraxin receptor in cerebrospinal fluid as a potential biomarker for neurodegenerative diseases. Brain Res 1265: 158-170. doi: 10.1016/j.brainres.2009.01.058
    [108] Xu PT, Li YJ, Qin XJ, et al. (2006) Differences in apolipoprotein E3/3 and E4/4 allele-specific gene expression in hippocampus in Alzheimer disease. Neurobiol Dis 21: 256-275. doi: 10.1016/j.nbd.2005.07.004
    [109] Abdi F, Quinn JF, Jankovic J, et al. (2006) Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders. J Alzheimers Dis 9: 293-348.
    [110] Weisel JW (2005) Fibrinogen and fibrin. Adv Protein Chem 70: 247-299. doi: 10.1016/S0065-3233(05)70008-5
    [111] Cortes-Canteli M, Strickland S (2009) Fibrinogen, a possible key player in Alzheimer's disease. J Thromb Haemost 7 Suppl 1: 146-150.
    [112] Cortes-Canteli M, Paul J, Norris EH, et al. (2010) Fibrinogen and beta-amyloid association alters thrombosis and fibrinolysis: a possible contributing factor to Alzheimer's disease. Neuron 66: 695-709. doi: 10.1016/j.neuron.2010.05.014
    [113] Ahn HJ, Glickman JF, Poon KL, et al. (2014) A novel Abeta-fibrinogen interaction inhibitor rescues altered thrombosis and cognitive decline in Alzheimer's disease mice. J Exp Med 211: 1049-1062. doi: 10.1084/jem.20131751
    [114] Ahn HJ, Zamolodchikov D, Cortes-Canteli M, et al. (2010) Alzheimer's disease peptide beta-amyloid interacts with fibrinogen and induces its oligomerization. Proc Natl Acad Sci U S A 107: 21812-21817. doi: 10.1073/pnas.1010373107
    [115] Mueller C, Zhou W, Vanmeter A, et al. (2010) The heme degradation pathway is a promising serum biomarker source for the early detection of Alzheimer's disease. J Alzheimers Dis 19: 1081-1091.
    [116] Langbein L, Heid HW, Moll I, et al. (1993) Molecular characterization of the body site-specific human epidermal cytokeratin 9: cDNA cloning, amino acid sequence, and tissue specificity of gene expression. Differentiation 55: 57-71. doi: 10.1111/j.1432-0436.1993.tb00033.x
    [117] Ghosh D, Lippert D, Krokhin O, et al. (2010) Defining the membrane proteome of NK cells. J Mass Spectrom 45: 1-25.
    [118] van Niel G, Raposo G, Candalh C, et al. (2001) Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121: 337-349. doi: 10.1053/gast.2001.26263
    [119] de Mateo S, Castillo J, Estanyol JM, et al. (2011) Proteomic characterization of the human sperm nucleus. Proteomics 11: 2714-2726. doi: 10.1002/pmic.201000799
    [120] Bohm D, Keller K, Pieter J, et al. (2012) Comparison of tear protein levels in breast cancer patients and healthy controls using a de novo proteomic approach. Oncol Rep 28: 429-438.
    [121] Kim YS, Gu BH, Choi BC, et al. (2013) Apolipoprotein A-IV as a novel gene associated with polycystic ovary syndrome. Int J Mol Med 31: 707-716.
    [122] Fu BS, Liu W, Zhang JW, et al. (2009) [Serum proteomic analysis on metastasis-associated proteins of hepatocellular carcinoma]. Nan Fang Yi Ke Da Xue Xue Bao 29: 1775-1778.
    [123] Li X, Long J, He T, et al. (2015) Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease. Sci Rep 5: 12393. doi: 10.1038/srep12393
    [124] Femminella GD, Ferrara N, Rengo G (2015) The emerging role of microRNAs in Alzheimer's disease. Front Physiol 6: 40.
    [125] Lukiw WJ, Zhao Y, Cui JG (2008) An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283: 31315-31322. doi: 10.1074/jbc.M805371200
    [126] Zhu HC, Wang LM, Wang M, et al. (2012) MicroRNA-195 downregulates Alzheimer's disease amyloid-beta production by targeting BACE1. Brain Res Bull 88: 596-601. doi: 10.1016/j.brainresbull.2012.05.018
    [127] Santa-Maria I, Alaniz ME, Renwick N, et al. (2015) Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau. J Clin Invest 125: 681-686. doi: 10.1172/JCI78421
    [128] Kosicek M, Zetterberg H, Andreasen N, et al. (2012) Elevated cerebrospinal fluid sphingomyelin levels in prodromal Alzheimer's disease. Neurosci Lett 516: 302-305. doi: 10.1016/j.neulet.2012.04.019
    [129] Mulder C, Wahlund LO, Teerlink T, et al. (2003) Decreased lysophosphatidylcholine/phosphatidylcholine ratio in cerebrospinal fluid in Alzheimer's disease. J Neural Transm (Vienna) 110: 949-955. doi: 10.1007/s00702-003-0007-9
    [130] Satoi H, Tomimoto H, Ohtani R, et al. (2005) Astroglial expression of ceramide in Alzheimer's disease brains: a role during neuronal apoptosis. Neuroscience 130: 657-666. doi: 10.1016/j.neuroscience.2004.08.056
    [131] Mapstone M, Cheema AK, Fiandaca MS, et al. (2014) Plasma phospholipids identify antecedent memory impairment in older adults. Nat Med 20: 415-418. doi: 10.1038/nm.3466
    [132] Wood PL, Medicherla S, Sheikh N, et al. (2015) Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer's Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer's Disease. J Alzheimers Dis 48: 537-546. doi: 10.3233/JAD-150336
    [133] Hu Z, Chang YC, Wang Y, et al. (2013) VisANT 4.0: Integrative network platform to connect genes, drugs, diseases and therapies. Nucleic Acids Res 41: W225-231. doi: 10.1093/nar/gkt401
    [134] Chatr-Aryamontri A, Breitkreutz BJ, Oughtred R, et al. (2015) The BioGRID interaction database: 2015 update. Nucleic Acids Res 43: D470-478. doi: 10.1093/nar/gku1204
    [135] Johnson C, Tinti M, Wood NT, et al. (2011) Visualization and biochemical analyses of the emerging mammalian 14-3-3-phosphoproteome. Mol Cell Proteomics 10: M110 005751.
    [136] Reddy A, Huang CC, Liu H, et al. (2010) Robust gene network analysis reveals alteration of the STAT5a network as a hallmark of prostate cancer. Genome Inform 24: 139-153.
    [137] Araujo DJ, Anderson AG, Berto S, et al. (2015) FoxP1 orchestration of ASD-relevant signaling pathways in the striatum. Genes Dev 29: 2081-2096. doi: 10.1101/gad.267989.115
    [138] Haas LT, Salazar SV, Kostylev MA, et al. (2015) Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease. Brain 139: 526-546.
    [139] Shahani N, Seshadri S, Jaaro-Peled H, et al. (2015) DISC1 regulates trafficking and processing of APP and Abeta generation. Mol Psychiatry 20: 874-879. doi: 10.1038/mp.2014.100
    [140] Croft D, O'Kelly G, Wu G, et al. (2011) Reactome: a database of reactions, pathways and biological processes. Nucleic Acids Res 39: D691-697. doi: 10.1093/nar/gkq1018
    [141] D'Eustachio P (2013) Pathway Databases: Making Chemical and Biological Sense of the Genomic Data Flood. Chem Biol 20: 629-635. doi: 10.1016/j.chembiol.2013.03.018
    [142] Wang X, Liotta L (2011) Clinical bioinformatics: a new emerging science. J Clin Bioinforma 1: 1. doi: 10.1186/2043-9113-1-1
    [143] Bellazzi R, Masseroli M, Murphy S, et al. (2012) Clinical Bioinformatics: challenges and opportunities. BMC Bioinform 13: 1-8. doi: 10.1186/1471-2105-13-1
    [144] Butte AJ (2008) Translational Bioinformatics: Coming of Age. J Am Med Inf Assoc 15: 709-714. doi: 10.1197/jamia.M2824
    [145] Larrañaga P, Calvo B, Santana R, et al. (2006) Machine learning in bioinformatics. Brief Bioinform 7: 86-112. doi: 10.1093/bib/bbk007
    [146] Pavlopoulos GA, Secrier M, Moschopoulos CN, et al. (2011) Using graph theory to analyze biological networks. BioData Min 4: 1-27. doi: 10.1186/1756-0381-4-1
    [147] Bullmore E, Sporns O (2009) Complex brain networks: graph theoretical analysis of structural and functional systems. Nat Rev Neurosci 10: 186-198. doi: 10.1038/nrn2575
    [148] Stam CJ (2014) Modern network science of neurological disorders. Nat Rev Neurosci 15: 683-695. doi: 10.1038/nrn3801
    [149] Baumgartner C, Osl M, Netzer M, et al. (2011) Bioinformatic-driven search for metabolic biomarkers in disease. J Clin Bioinforma 1: 1-10. doi: 10.1186/2043-9113-1-1
    [150] Inza I, Calvo B, Armañanzas R, et al. (2010) Machine Learning: An Indispensable Tool in Bioinformatics. In: Matthiesen R, editor. Bioinformatics Methods in Clinical Research: Humana Press. pp. 25-48.
    [151] Guyon I, Weston J, Barnhill S, et al. Gene Selection for Cancer Classification using Support Vector Machines. Mach Learn 46: 389-422.
    [152] Hsu W-C, Denq C, Chen S-S (2013) A diagnostic methodology for Alzheimer’s disease. J Clin Bioinforma 3: 1-13.
    [153] Horwitz B, Rowe JB (2011) Functional biomarkers for neurodegenerative disorders based on the network paradigm. Prog Neurobiol 95: 505-509. doi: 10.1016/j.pneurobio.2011.07.005
    [154] de Haan W, Pijnenburg YAL, Strijers RLM, et al. (2009) Functional neural network analysis in frontotemporal dementia and Alzheimer's disease using EEG and graph theory. BMC Neurosci 10: 101-101. doi: 10.1186/1471-2202-10-101
    [155] Brier MR, Thomas JB, Fagan AM, et al. (2014) Functional connectivity and graph theory in preclinical Alzheimer's disease. Neurobiol Aging 35: 757-768. doi: 10.1016/j.neurobiolaging.2013.10.081
    [156] Zhang D, Wang Y, Zhou L, et al. (2011) Multimodal classification of Alzheimer's disease and mild cognitive impairment. NeuroImage 55: 856-867. doi: 10.1016/j.neuroimage.2011.01.008
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