Alzheimer's disease (Homo sapiens)

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1, 3, 8, 11, 13...102220294, 591919122, 7, 22422Mitochondrial dysfunctionsAPP-alphaEndoplasmic reticulum (ER)NeuronAggr. amyloidalpha-Secretasep-Amyloid Beta (AB)MicrogliaOligomeric intracellular ABLower energy production?AICDATP depletionMitochondiral dysfunctionCell deathNeuronal InjuryC83Calcium overloadApoptosisJAK-STATIP3NF-kB Modulation of gene expressionNOAPPHydrogen peroxideProteinOxidative PhosphorylationProtein oxidationCalciumCopperIronCalcium Signaling PathwayRAGEInduction of ApoptosisAPPBP1MIR101666APBB1GAPDHADAM10BACE1PSENENPSEN1NCSTNAPH1AIDEMMELPLAPOELRP1FASTNFRSF1AFADDCASP8Cx ICx IICx IIICx IVCx VAPP processingbeta-Secretasegamma-SecretaseHSD17B10Fall in mitochondrialsAPP-betaC99membrane potentialIncreased ROSDegredationInactivationBIDCYCSCALM1CHPBADCALM2CALM3CALML3CALML5PPP3CAPPP3CBPPP3CCPPP3R1PPP3R2CHP2ADAM17PSEN2APAF1CASP9CASP3AB AggregationOligomeric ABalpha-synucleinSNCASenileplaqueNACGPCRGRIN1CACNA1CGRIN2AGRIN2BGRIN2CGRIN2DCACNA1DCACNA1FCACNA1SGNAQPLCB1PLCB2PLCB3PLCB4TNFIL1BMAPK1MAPK3CASP12ApoptosisRYR3PSENENATP2A2ATP2A1ATP2A3EIF2AK3ERN1ATF6ITPR1ITPR2ITPR3CalciumCalciumER stressCAPN1CAPN2TP53CDK5R1NOS1CDK5TAUPPGSK3BCASP3CASP7Paired helical filaments (PHFs)Neurofibrillarytangles (NFTs)ABApoptosisDNA damageInflammationLipid peroxidationONOO-Based on Table 1 from Burgos et al, PLoS ONE 2014 May.15miRNA 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)MIR219-2MIR22MIR125B1MIR1307MIR34CMIR34BMIR887MIR182MIR135A1MIR135A2MIR184MIR127MIR30C2MIR873MIR125AMIR671MIR21MIR1285-2MIR375MIR3176MIR124-3MIR29AMIR29B1MIR29CMIR132MIR34CMIR375MIR124-3MIR9-1MIR138-2MIR138-2MIR132MIR21MIR21MIR21MIR21MIR21MIR1285-2AB


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. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms



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  1. Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH; ''Neurotoxicity induces cleavage of p35 to p25 by calpain.''; Nature, 2000 PubMed Europe PMC Scholia
  2. 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 Europe PMC Scholia
  3. Bezprozvanny I, Mattson MP; ''Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.''; Trends Neurosci, 2008 PubMed Europe PMC Scholia
  4. 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 Europe PMC Scholia
  5. 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 Europe PMC Scholia
  6. Parihar MS, Hemnani T; ''Alzheimer's disease pathogenesis and therapeutic interventions.''; J Clin Neurosci, 2004 PubMed Europe PMC Scholia
  7. 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 Europe PMC Scholia
  8. Small DH, Mok SS, Bornstein JC; ''Alzheimer's disease and Abeta toxicity: from top to bottom.''; Nat Rev Neurosci, 2001 PubMed Europe PMC Scholia
  9. 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 Europe PMC Scholia
  10. 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 Europe PMC Scholia
  11. Takuma K, Yan SS, Stern DM, Yamada K; ''Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.''; J Pharmacol Sci, 2005 PubMed Europe PMC Scholia
  12. 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 Europe PMC Scholia
  13. 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 Europe PMC Scholia
  14. Delay C, Mandemakers W, Hébert SS; ''MicroRNAs in Alzheimer's disease.''; Neurobiol Dis, 2012 PubMed Europe PMC Scholia
  15. 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 Europe PMC Scholia
  16. Dickson DW; ''Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?''; J Clin Invest, 2004 PubMed Europe PMC Scholia
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  20. 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 Europe PMC Scholia
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116396view23:18, 6 May 2021EweitzModified title
115412view11:55, 18 February 2021EgonwMade five more pathways clickable
108233view14:43, 1 December 2019EgonwBetter point to a pathway than a inhibitor metabolite.
108214view11:18, 29 November 2019FehrhartOntology Term : 'DOID:10652' removed !
108091view11:56, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
106706view13:13, 17 September 2019MaintBotHMDB identifier normalization
106521view23:41, 5 September 2019KhanspersModified description
105877view04:50, 16 August 2019KhanspersModified description
105524view05:58, 9 August 2019KhanspersModified description
104977view18:27, 27 June 2019Khanspersremoved KEGG
104976view18:26, 27 June 2019KhanspersModified description
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

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)
JAK-STATMetaboliteCHEBI:76617 (ChEBI)
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)
MIR29AGeneProductENSG00000284032 (Ensembl)
MIR29B1GeneProduct407024 (Entrez Gene)
MIR29CGeneProductENSG00000284214 (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)
NF-kB MetaboliteQ27087912 (Wikidata)
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
RAGEProteinQ15109 (Uniprot-TrEMBL)
RYR3GeneProductENSG00000198838 (Ensembl)
SNCAGeneProductENSG00000145335 (Ensembl)
TAUGeneProductENSG00000186868 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
TNFRSF1AGeneProductENSG00000067182 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)

Annotated Interactions

No annotated interactions

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