Alzheimers Disease (Homo sapiens)

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1-3, 6-10, 12...214, 181526142111, 21, 24182528528Endoplasmic reticulum (ER)Lower energy production?alpha-SecretaseMitochondrial dysfunctionCell deathMicrogliaAICDCalcium overloadOligomeric intracellular ABATP depletionNeuronal InjurysAPP-alphaNeuronC83Mitochondiral dysfunctionp-Amyloid Beta (AB)Aggr. amyloidNOCalcium Signaling PathwayMIR101Modulation of gene expressionAPPBP1Induction of ApoptosisApoptosisCopperProtein oxidationIP3IronAPPHydrogen peroxideCalciumOxidative PhosphorylationAPBB1GAPDHADAM10BACE1PSENENPSEN1NCSTNAPH1AIDEMMELPLAPOELRP1FASTNFRSF1AFADDCASP8Cx ICx IICx IIICx IVCx VAPP processingbeta-Secretasegamma-SecretaseHSD17B10Fall in mitochondrialsAPP-betaC99membrane potentialIncreased ROSDegredationInactivationBIDCYCSCALM1CHPBADCALM2CALM3CALML3CALML5PPP3CAPPP3CBPPP3CCPPP3R1PPP3R2CHP2ADAM17PSEN2APAF1CASP9CASP3AB AggregationOligomeric ABalpha-synucleinSNCASenileplaqueNACGPCRGRIN1CACNA1CGRIN2AGRIN2BGRIN2CGRIN2DCACNA1DCACNA1FCACNA1SGNAQPLCB1PLCB2PLCB3PLCB4TNFIL1BMAPK1MAPK3CASP12ApoptosisRYR3PSENENATP2A2ATP2A1ATP2A3EIF2AK3ERN1ATF6ITPR1ITPR2ITPR3CalciumCalciumER stressCAPN1CAPN2TP53CDK5R1NOS1CDK5TAUGSK3BPPCASP3CASP7Paired helical filaments (PHFs)Neurofibrillarytangles (NFTs)ABApoptosisDNA damageInflammationLipid peroxidationONOO-Based on Table 1 from Burgos et al, PLoS ONE 2014 May.16miRNA differentially expressed in AD(measured in cerebrospinal fluid)MIR199BMIR381MIR181B1MIR124-2MIR181DMIR124-1MIR760MIR184MIR136MIR181A1MIR598MIR181A2MIR127MIR34BMIR101-1MIR95MIR488MIR138-2MIR769MIR218-1MIR181B2MIR138-1MIR218-2MIR495MIR708MIR874MIR873MIR129-1MIR129-2MIR139MIR3200MIR431MIR9-1MIR9-2MIR9-3MIR326MIR377MIR433MIR323AMIR134MIR329-1MIR329-2MIR10AMIR33BMIR410MIR708miRNA differentially expressed in AD(measured in blood serum)MIR219-2MIR22MIR125B1MIR1307MIR34CMIR34BMIR887MIR182MIR135A1MIR135A2MIR184MIR127MIR30C2MIR873MIR125AMIR671MIR21MIR1285-2MIR375MIR3176MIR124-3MIR29AMIR29B1MIR29CMIR132MIR34CMIR375MIR124-3MIR9-1MIR138-2MIR138-2MIR132MIR21MIR21MIR21MIR21MIR21MIR1285-2


This pathway displays current genes, proteolytic events and other processes associated with the progression of Alzheimer's disease. This pathway was adapted from KEGG on 10/7/2011. Note: mitochondrial associated genes Cx I through Cx V are not currently included, as these correspond to over a hundred distinct factors. See below source URL for more information. Source: KEGG (


Adapted from KEGG

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Ontology Terms



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  1. Small DH, Mok SS, Bornstein JC; ''Alzheimer's disease and Abeta toxicity: from top to bottom.''; Nat Rev Neurosci, 2001 PubMed
  2. Chan XH, Nama S, Gopal F, Rizk P, Ramasamy S, Sundaram G, Ow GS, Ivshina AV, Tanavde V, Haybaeck J, Kuznetsov V, Sampath P; ''Targeting glioma stem cells by functional inhibition of a prosurvival oncomiR-138 in malignant gliomas.''; Cell Rep, 2012 PubMed
  3. Hölscher C; ''Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis.''; Neurobiol Dis, 1998 PubMed
  4. Delay C, Mandemakers W, Hébert SS; ''MicroRNAs in Alzheimer's disease.''; Neurobiol Dis, 2012 PubMed
  5. Hébert SS, Horré K, Nicolaï L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN, Kauppinen S, Delacourte A, De Strooper B; ''Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression.''; Proc Natl Acad Sci U S A, 2008 PubMed
  6. Piras S, Furfaro AL, Domenicotti C, Traverso N, Marinari UM, Pronzato MA, Nitti M; ''RAGE Expression and ROS Generation in Neurons: Differentiation versus Damage.''; Oxid Med Cell Longev, 2016 PubMed
  7. Abdelmohsen K, Hutchison ER, Lee EK, Kuwano Y, Kim MM, Masuda K, Srikantan S, Subaran SS, Marasa BS, Mattson MP, Gorospe M; ''miR-375 inhibits differentiation of neurites by lowering HuD levels.''; Mol Cell Biol, 2010 PubMed
  8. Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A; ''Presenilin-mediated signal transduction.''; Physiol Behav, 2007 PubMed
  9. Tian S, Huang S, Wu S, Guo W, Li J, He X; ''MicroRNA-1285 inhibits the expression of p53 by directly targeting its 3' untranslated region.''; Biochem Biophys Res Commun, 2010 PubMed
  10. Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP; ''MicroRNA targeting specificity in mammals: determinants beyond seed pairing.''; Mol Cell, 2007 PubMed
  11. Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M; ''Induction of neuronal death by ER stress in Alzheimer's disease.''; J Chem Neuroanat, 2004 PubMed
  12. Terao M, Fratelli M, Kurosaki M, Zanetti A, Guarnaccia V, Paroni G, Tsykin A, Lupi M, Gianni M, Goodall GJ, Garattini E; ''Induction of miR-21 by retinoic acid in estrogen receptor-positive breast carcinoma cells: biological correlates and molecular targets.''; J Biol Chem, 2011 PubMed
  13. Avila J; ''Tau phosphorylation and aggregation in Alzheimer's disease pathology.''; FEBS Lett, 2006 PubMed
  14. Reese LC, Zhang W, Dineley KT, Kayed R, Taglialatela G; ''Selective induction of calcineurin activity and signaling by oligomeric amyloid beta.''; Aging Cell, 2008 PubMed
  15. Burgos K, Malenica I, Metpally R, Courtright A, Rakela B, Beach T, Shill H, Adler C, Sabbagh M, Villa S, Tembe W, Craig D, Van Keuren-Jensen K; ''Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.''; PLoS One, 2014 PubMed
  16. Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH; ''Neurotoxicity induces cleavage of p35 to p25 by calpain.''; Nature, 2000 PubMed
  17. Bojarski L, Herms J, Kuznicki J; ''Calcium dysregulation in Alzheimer's disease.''; Neurochem Int, 2008 PubMed
  18. Bezprozvanny I, Mattson MP; ''Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.''; Trends Neurosci, 2008 PubMed
  19. Zhou X, Ren Y, Moore L, Mei M, You Y, Xu P, Wang B, Wang G, Jia Z, Pu P, Zhang W, Kang C; ''Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status.''; Lab Invest, 2010 PubMed
  20. Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC; ''MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1.''; Stem Cells Dev, 2011 PubMed
  21. Dickson DW; ''Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?''; J Clin Invest, 2004 PubMed
  22. Papagiannakopoulos T, Shapiro A, Kosik KS; ''MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells.''; Cancer Res, 2008 PubMed
  23. Shen Y, He P, Zhong Z, McAllister C, Lindholm K; ''Distinct destructive signal pathways of neuronal death in Alzheimer's disease.''; Trends Mol Med, 2006 PubMed
  24. Mattson MP; ''Pathways towards and away from Alzheimer's disease.''; Nature, 2004 PubMed
  25. Parihar MS, Hemnani T; ''Alzheimer's disease pathogenesis and therapeutic interventions.''; J Clin Neurosci, 2004 PubMed
  26. Hauptmann S, Keil U, Scherping I, Bonert A, Eckert A, Müller WE; ''Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease.''; Exp Gerontol, 2006 PubMed
  27. Takuma K, Yan SS, Stern DM, Yamada K; ''Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.''; J Pharmacol Sci, 2005 PubMed
  28. Gandy S; ''The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease.''; J Clin Invest, 2005 PubMed
  29. Wu H, Huang M, Lu M, Zhu W, Shu Y, Cao P, Liu P; ''Regulation of microtubule-associated protein tau (MAPT) by miR-34c-5p determines the chemosensitivity of gastric cancer to paclitaxel.''; Cancer Chemother Pharmacol, 2013 PubMed
  30. Ivins KJ, Thornton PL, Rohn TT, Cotman CW; ''Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.''; Neurobiol Dis, 1999 PubMed


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102211view00:06, 11 December 2018Khanspersfixed unconnected interaction
102163view22:07, 4 December 2018Khanspersupdated xrefs for miRNAs
101829view09:35, 12 November 2018EgonwReplaced an old Uniprot data source with the new one.
99069view14:16, 29 October 2018SusanFixed interactions
99043view10:32, 27 October 2018Lovnish.thakurReverted to version '10:25, 27 October 2018' by Lovnish.thakur
99042view10:31, 27 October 2018Lovnish.thakurIncluded RAGE(Receptor for glycosylation end products)interaction with Aβ
99041view10:25, 27 October 2018Lovnish.thakurI have included the Receptor for advanced glycosylation end products(RAGE)in this pathway.Interaction of RAGE with Abeta is also responsible for neuronal damage & inflamation mediated which is mediated by NF-κB & JAK/STAT signaling pathways.
97494view14:02, 23 May 2018Fehrhartfixed connections
97492view13:57, 23 May 2018Fehrhartfixed connections
97491view13:56, 23 May 2018Fehrhartfixed connections
87372view09:56, 22 July 2016MaintBotadded missing graphids
85192view16:05, 23 April 2016EgonwReplaced a mim-conversion with Arrow.
85191view16:01, 23 April 2016EgonwFixed a weird char in a reference.
82906view15:21, 11 November 2015JmeliusCorrect outdated id
79765view02:16, 11 April 2015AlexanderPicoAdded miRNA interactions and refs
79302view19:04, 20 March 2015AlexanderPicoupdated miRNA label
78941view22:47, 16 February 2015KhanspersAdded mir132
78916view21:58, 13 February 2015KhanspersAdded lit ref for mir29
78915view21:54, 13 February 2015KhanspersSpecify description
78914view21:41, 13 February 2015Khanspersfixed incorrect lit ref
78913view21:33, 13 February 2015KhanspersAdded related miRNAs
78911view18:50, 12 February 2015KhanspersAdded mir101
78488view10:28, 7 January 2015MaintBotadded missing graphIds
75217view20:21, 9 May 2014KhanspersAdding lit refs
75209view20:04, 9 May 2014KhanspersAdded states, fixed missing xrefs, changed some pathway nodes to labels
71384view18:40, 17 October 2013MaintBotAutomated update of data sources
63153view20:17, 8 May 2013MaintBotUpdating GPML version
59190view19:07, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45384view03:10, 8 October 2011NsalomonisAdded missing edges
45375view21:24, 7 October 2011KhanspersModified categories
45313view20:05, 7 October 2011NsalomonisModified description
45307view20:04, 7 October 2011NsalomonisModified description
45302view20:01, 7 October 2011Nsalomonisfinished initial layout
45300view19:49, 7 October 2011NsalomonisSpecify description
45299view19:44, 7 October 2011NsalomonisPeriodical save, work in progress
45298view19:38, 7 October 2011NsalomonisSpecify description
45297view19:34, 7 October 2011NsalomonisPeriodical save, work in progress
45267view18:48, 7 October 2011NsalomonisSpecify description
45259view18:44, 7 October 2011NsalomonisPeriodical save, work in progress
45240view18:22, 7 October 2011NsalomonisSpecify description
45237view18:13, 7 October 2011NsalomonisPeriodical save, work in progress
45236view18:12, 7 October 2011NsalomonisSpecify description
45235view17:53, 7 October 2011NsalomonisPeriodical save, work in progress
45232view17:43, 7 October 2011NsalomonisPeriodical save, work in progress
45224view17:33, 7 October 2011NsalomonisPeriodical save, work in progress
45210view17:23, 7 October 2011NsalomonisPeriodical save, work in progress
45206view17:13, 7 October 2011NsalomonisPeriodical save, work in progress
45205view17:02, 7 October 2011NsalomonisPeriodical save, work in progress
45169view06:40, 7 October 2011ThomasOntology Term : 'Alzheimers Dementia' added !
45168view06:40, 7 October 2011ThomasOntology Term : 'Alzheimer disease pathway' added !

External references


View all...
NameTypeDatabase referenceComment
ADAM10GeneProductENSG00000137845 (Ensembl)
ADAM17GeneProductENSG00000151694 (Ensembl)
APAF1GeneProductENSG00000120868 (Ensembl)
APBB1GeneProductENSG00000166313 (Ensembl)
APH1AGeneProductENSG00000117362 (Ensembl)
APOEGeneProductENSG00000130203 (Ensembl)
APP processingPathway
APPBP1GeneProductENSG00000159593 (Ensembl)
APPGeneProductENSG00000142192 (Ensembl)
ATF6GeneProductENSG00000118217 (Ensembl)
ATP2A1GeneProductENSG00000196296 (Ensembl)
ATP2A2GeneProductENSG00000174437 (Ensembl)
ATP2A3GeneProductENSG00000074370 (Ensembl)
ApoptosisPathwayWP254 (WikiPathways)
BACE1GeneProductENSG00000186318 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BIDGeneProductENSG00000015475 (Ensembl)
CACNA1CGeneProductENSG00000151067 (Ensembl)
CACNA1DGeneProductENSG00000157388 (Ensembl)
CACNA1FGeneProductENSG00000102001 (Ensembl)
CACNA1SGeneProductENSG00000081248 (Ensembl)
CALM1GeneProductENSG00000198668 (Ensembl)
CALM2GeneProductENSG00000143933 (Ensembl)
CALM3GeneProductENSG00000160014 (Ensembl)
CALML3GeneProductENSG00000178363 (Ensembl)
CALML5GeneProductENSG00000178372 (Ensembl)
CAPN1GeneProductENSG00000014216 (Ensembl)
CAPN2GeneProductENSG00000162909 (Ensembl)
CASP12GeneProductENSG00000204403 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CASP7GeneProductENSG00000165806 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CDK5GeneProductENSG00000164885 (Ensembl)
CDK5R1GeneProductENSG00000176749 (Ensembl)
CHPGeneProduct11261 (Entrez Gene)
CHP2GeneProduct63928 (Entrez Gene)
CYCSGeneProductENSG00000172115 (Ensembl)
Calcium Signaling PathwayPathway
CalciumMetaboliteHMDB00464 (HMDB)
CopperMetaboliteHMDB00657 (HMDB)
Cx IGeneProduct
Cx IIGeneProduct
Cx IIIGeneProduct
Cx IVGeneProduct
Cx VGeneProduct
DNA damagePathway
EIF2AK3GeneProductENSG00000172071 (Ensembl)
ERN1GeneProductENSG00000178607 (Ensembl)
FADDGeneProductENSG00000168040 (Ensembl)
FASGeneProductENSG00000026103 (Ensembl)
GAPDHGeneProductENSG00000111640 (Ensembl)
GNAQGeneProductENSG00000156052 (Ensembl)
GRIN1GeneProductENSG00000176884 (Ensembl)
GRIN2AGeneProductENSG00000183454 (Ensembl)
GRIN2BGeneProductENSG00000273079 (Ensembl)
GRIN2CGeneProductENSG00000161509 (Ensembl)
GRIN2DGeneProductENSG00000105464 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
HSD17B10GeneProductENSG00000072506 (Ensembl)
Hydrogen peroxideMetaboliteHMDB03125 (HMDB)
IDEGeneProductENSG00000119912 (Ensembl)
IL1BGeneProductENSG00000125538 (Ensembl)
IP3MetaboliteHMDB01498 (HMDB)
ITPR1GeneProductENSG00000150995 (Ensembl)
ITPR2GeneProductENSG00000123104 (Ensembl)
ITPR3GeneProductENSG00000096433 (Ensembl)
Induction of ApoptosisPathwayWP1896 (WikiPathways)
InflammationPathwayWP453 (WikiPathways)
IronMetaboliteHMDB00692 (HMDB)
LPLGeneProductENSG00000175445 (Ensembl)
LRP1GeneProductENSG00000123384 (Ensembl)
Lipid peroxidationPathwayWP1878 (WikiPathways)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MIR101-1Rna406893 (Entrez Gene)
MIR101GeneProductENSG00000199135 (Ensembl)
MIR10ARna406902 (Entrez Gene)
MIR124-1Rna406907 (Entrez Gene)
MIR124-2Rna406908 (Entrez Gene)
MIR124-3Rna406909 (Entrez Gene)
MIR125ARna406910 (Entrez Gene)
MIR125B1Rna406911 (Entrez Gene)
MIR127RnaENSG00000207608 (Ensembl)
MIR1285-2Rna100302268 (Entrez Gene)
MIR129-1Rna406917 (Entrez Gene)
MIR129-2RnaENSG00000199077 (Ensembl)
MIR1307Rna100302174 (Entrez Gene)
MIR132GeneProduct406921 (Entrez Gene)
MIR134Rna406924 (Entrez Gene)
MIR135A1Rna406925 (Entrez Gene)
MIR135A2Rna406926 (Entrez Gene)
MIR136RnaENSG00000207942 (Ensembl)
MIR138-1Rna406929 (Entrez Gene)
MIR138-2Rna406930 (Entrez Gene)
MIR138-2RnaENSG00000207649 (Ensembl)
MIR139Rna406931 (Entrez Gene)
MIR181A1Rna406995 (Entrez Gene)
MIR181A2Rna406954 (Entrez Gene)
MIR181B1Rna406955 (Entrez Gene)
MIR181B2Rna406956 (Entrez Gene)
MIR181DRna574457 (Entrez Gene)
MIR182Rna406958 (Entrez Gene)
MIR184Rna406960 (Entrez Gene)
MIR199BRna406978 (Entrez Gene)
MIR21Rna406991 (Entrez Gene)
MIR218-1Rna407000 (Entrez Gene)
MIR218-2Rna407001 (Entrez Gene)
MIR219-2Rna407003 (Entrez Gene)
MIR22RnaENSG00000275595 (Ensembl)
MIR29AGeneProductENSG00000277934 (Ensembl)
MIR29B1GeneProduct407024 (Entrez Gene)
MIR29CGeneProductENSG00000275668 (Ensembl)
MIR30C2RnaENSG00000199094 (Ensembl)
MIR3176Rna100423037 (Entrez Gene)
MIR3200Rna100422912 (Entrez Gene)
MIR323ARnaENSG00000199069 (Ensembl)
MIR326Rna442900 (Entrez Gene)
MIR329-1RnaENSG00000207761 (Ensembl)
MIR329-2Rna574409 (Entrez Gene)
MIR33BRna693120 (Entrez Gene)
MIR34BRnaENSG00000207811 (Ensembl)
MIR34CRna407042 (Entrez Gene)
MIR34CRnaENSG00000207562 (Ensembl)
MIR375RnaENSG00000198973 (Ensembl)
MIR377RnaENSG00000199015 (Ensembl)
MIR381RnaENSG00000199020 (Ensembl)
MIR410RnaENSG00000199092 (Ensembl)
MIR431Rna574038 (Entrez Gene)
MIR433RnaENSG00000207569 (Ensembl)
MIR488RnaENSG00000202609 (Ensembl)
MIR495RnaENSG00000207743 (Ensembl)
MIR598RnaENSG00000207600 (Ensembl)
MIR671Rna768213 (Entrez Gene)
MIR708Rna100126333 (Entrez Gene)
MIR760RnaENSG00000211575 (Ensembl)
MIR769Rna768217 (Entrez Gene)
MIR873RnaENSG00000215939 (Ensembl)
MIR874RnaENSG00000216009 (Ensembl)
MIR887RnaENSG00000216077 (Ensembl)
MIR9-1Rna407046 (Entrez Gene)
MIR9-1RnaENSG00000207933 (Ensembl)
MIR9-2Rna407047 (Entrez Gene)
MIR9-3Rna407051 (Entrez Gene)
MIR95Rna407052 (Entrez Gene)
MMEGeneProductENSG00000196549 (Ensembl)
Modulation of gene expressionPathwayWP1821 (WikiPathways)
NCSTNGeneProductENSG00000162736 (Ensembl)
NOMetaboliteHMDB03378 (HMDB)
NOS1GeneProductENSG00000089250 (Ensembl)
ONOO-MetaboliteHMDB02179 (HMDB)
Oxidative PhosphorylationPathwayWP623 (WikiPathways)
PLCB1GeneProductENSG00000182621 (Ensembl)
PLCB2GeneProductENSG00000137841 (Ensembl)
PLCB3GeneProductENSG00000149782 (Ensembl)
PLCB4GeneProductENSG00000101333 (Ensembl)
PPP3CAGeneProductENSG00000138814 (Ensembl)
PPP3CBGeneProductENSG00000107758 (Ensembl)
PPP3CCGeneProductENSG00000120910 (Ensembl)
PPP3R1GeneProductENSG00000221823 (Ensembl)
PPP3R2GeneProductENSG00000188386 (Ensembl)
PSEN1GeneProductENSG00000080815 (Ensembl)
PSEN2GeneProductENSG00000143801 (Ensembl)
PSENENGeneProductENSG00000205155 (Ensembl)
Protein oxidationPathway
RYR3GeneProductENSG00000198838 (Ensembl)
SNCAGeneProductENSG00000145335 (Ensembl)
TAUGeneProductENSG00000186868 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
TNFRSF1AGeneProductENSG00000067182 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)

Annotated Interactions

No annotated interactions
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