Alzheimers Disease (Homo sapiens)

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Neuron Aggr. amyloid Endoplasmic reticulum (ER) Calcium overload Cell death ATP depletion Neuronal Injury Mitochondiral dysfunction AICD C83 Amyloid Beta (AB) alpha-Secretase Microglia Oligomeric intracellular AB p- Lower energy production? sAPP-alpha Mitochondrial dysfunction Protein oxidation Apoptosis DNA damage Inflammation Lipid peroxidation NO Iron Apoptosis Hydrogen peroxide APPBP1 APP Oxidative Phosphorylation Calcium Signaling Pathway IP3 Copper Calcium MIR101 Induction of Apoptosis Modulation of gene expression APBB1 GAPDH ADAM10 ADAM17 BACE1 PSENEN PSEN1 NCSTN APH1A PSEN2 IDE MME LPL APOE LRP1 FAS TNFRSF1A FADD CASP8 Cx I Cx II Cx III Cx IV Cx V APP processing beta-Secretase gamma-Secretase HSD17B10 Fall in mitochondrial sAPP-beta C99 membrane potential Increased ROS Degredation Inactivation BID CYCS CALM1 CALM2 CALM3 CALML3 CALML5 CHP PPP3CA PPP3CB PPP3CC PPP3R1 PPP3R2 CHP2 BAD APAF1 CASP9 CASP3 AB Aggregation Oligomeric AB alpha-synuclein SNCA Senile plaque NAC GPCR GRIN1 GRIN2A GRIN2B GRIN2C GRIN2D CACNA1C CACNA1D CACNA1F CACNA1S GNAQ PLCB1 PLCB2 PLCB3 PLCB4 TNF IL1B MAPK1 MAPK3 CASP12 Apoptosis RYR3 PSENEN ATP2A2 ATP2A1 ATP2A3 EIF2AK3 ERN1 ATF6 ITPR1 ITPR2 ITPR3 Calcium Calcium ER stress CAPN1 CAPN2 TP53 CDK5R1 NOS1 CDK5 P P TAU GSK3B CASP3 CASP7 Paired helical filaments (PHFs) Neurofibrillary tangles (NFTs) AB ONOO- Based on Table 1 from Burgos et al, PLoS ONE 2014 May. miRNA differentially expressed in AD (measured in cerebrospinal fluid) MIR199B MIR381 MIR181B1 MIR124-2 MIR181D MIR124-1 MIR760 MIR184 MIR136 MIR181A1 MIR598 MIR181A2 MIR127 MIR34B MIR101-1 MIR95 MIR488 MIR138-2 MIR769 MIR218-1 MIR181B2 MIR138-1 MIR218-2 MIR495 MIR708 MIR874 MIR873 MIR129-1 MIR129-2 MIR139 MIR3200 MIR431 MIR9-1 MIR9-2 MIR9-3 MIR326 MIR377 MIR433 MIR323A MIR134 MIR329-1 MIR329-2 MIR10A MIR33B MIR410 MIR708 miRNA differentially expressed in AD (measured in blood serum) MIR219-2 MIR22 MIR125B1 MIR1307 MIR34C MIR34B MIR887 MIR182 MIR135A1 MIR135A2 MIR184 MIR127 MIR30C2 MIR873 MIR125A MIR671 MIR21 MIR1285-2 MIR375 MIR3176 MIR124-3 MIR132 MIR29A MIR29B1 MIR29C MIR34C MIR375 MIR124-3 MIR9-1 MIR138-2 MIR138-2 MIR132 MIR21 MIR21 MIR21 MIR21 MIR21 MIR1285-2 Name: Alzheimers Disease Last Modified: 10/17/2013 Organism: Homo sapiens


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 (

Quality Tags

Ontology Terms



  1. Parihar MS, Hemnani T; ''Alzheimer's disease pathogenesis and therapeutic interventions.''; J Clin Neurosci, 2004 PubMed
  2. 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
  3. Avila J; ''Tau phosphorylation and aggregation in Alzheimer's disease pathology.''; FEBS Lett, 2006 PubMed
  4. 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
  5. 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
  6. Gandy S; ''The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease.''; J Clin Invest, 2005 PubMed
  7. Ivins KJ, Thornton PL, Rohn TT, Cotman CW; ''Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.''; Neurobiol Dis, 1999 PubMed
  8. Bezprozvanny I, Mattson MP; ''Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.''; Trends Neurosci, 2008 PubMed
  9. Small DH, Mok SS, Bornstein JC; ''Alzheimer's disease and Abeta toxicity: from top to bottom.''; Nat Rev Neurosci, 2001 PubMed
  10. 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
  11. 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
  12. Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH; ''Neurotoxicity induces cleavage of p35 to p25 by calpain.''; Nature, 2000 PubMed
  13. 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
  14. 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
  15. 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
  16. 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
  17. Dickson DW; ''Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?''; J Clin Invest, 2004 PubMed
  18. Delay C, Mandemakers W, Hébert SS; ''MicroRNAs in Alzheimer's disease.''; Neurobiol Dis, 2012 PubMed
  19. Bojarski L, Herms J, Kuznicki J; ''Calcium dysregulation in Alzheimer's disease.''; Neurochem Int, 2008 PubMed
  20. Takuma K, Yan SS, Stern DM, Yamada K; ''Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.''; J Pharmacol Sci, 2005 PubMed
  21. Papagiannakopoulos T, Shapiro A, Kosik KS; ''MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells.''; Cancer Res, 2008 PubMed
  22. 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
  23. Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A; ''Presenilin-mediated signal transduction.''; Physiol Behav, 2007 PubMed
  24. 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
  25. 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
  26. 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
  27. Mattson MP; ''Pathways towards and away from Alzheimer's disease.''; Nature, 2004 PubMed
  28. 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
  29. Hölscher C; ''Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis.''; Neurobiol Dis, 1998 PubMed
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97494view 07:02, 23 May 2018Fehrhartfixed connections
97492view 06:57, 23 May 2018Fehrhartfixed connections
97491view 06:56, 23 May 2018Fehrhartfixed connections
87372view 02:56, 22 July 2016MaintBotadded missing graphids
85192view 09:05, 23 April 2016EgonwReplaced a mim-conversion with Arrow.
85191view 09:01, 23 April 2016EgonwFixed a weird char in a reference.
82906view 08:21, 11 November 2015JmeliusCorrect outdated id
79765view 19:16, 10 April 2015AlexanderPicoAdded miRNA interactions and refs
79302view 12:04, 20 March 2015AlexanderPicoupdated miRNA label
78941view 15:47, 16 February 2015KhanspersAdded mir132
78916view 14:58, 13 February 2015KhanspersAdded lit ref for mir29
78915view 14:54, 13 February 2015KhanspersSpecify description
78914view 14:41, 13 February 2015Khanspersfixed incorrect lit ref
78913view 14:33, 13 February 2015KhanspersAdded related miRNAs
78911view 11:50, 12 February 2015KhanspersAdded mir101
78488view 03:28, 7 January 2015MaintBotadded missing graphIds
75217view 13:21, 9 May 2014KhanspersAdding lit refs
75209view 13:04, 9 May 2014KhanspersAdded states, fixed missing xrefs, changed some pathway nodes to labels
71384view 11:40, 17 October 2013MaintBotAutomated update of data sources
63153view 13:17, 8 May 2013MaintBotUpdating GPML version
59190view 12:07, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
45384view 20:10, 7 October 2011NsalomonisAdded missing edges
45375view 14:24, 7 October 2011KhanspersModified categories
45313view 13:05, 7 October 2011NsalomonisModified description
45307view 13:04, 7 October 2011NsalomonisModified description
45302view 13:01, 7 October 2011Nsalomonisfinished initial layout
45300view 12:49, 7 October 2011NsalomonisSpecify description
45299view 12:44, 7 October 2011NsalomonisPeriodical save, work in progress
45298view 12:38, 7 October 2011NsalomonisSpecify description
45297view 12:34, 7 October 2011NsalomonisPeriodical save, work in progress
45267view 11:48, 7 October 2011NsalomonisSpecify description
45259view 11:44, 7 October 2011NsalomonisPeriodical save, work in progress
45240view 11:22, 7 October 2011NsalomonisSpecify description
45237view 11:13, 7 October 2011NsalomonisPeriodical save, work in progress
45236view 11:12, 7 October 2011NsalomonisSpecify description
45235view 10:53, 7 October 2011NsalomonisPeriodical save, work in progress
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45205view 10:02, 7 October 2011NsalomonisPeriodical save, work in progress
45169view 23:40, 6 October 2011ThomasOntology Term : 'Alzheimers Dementia' added !
45168view 23:40, 6 October 2011ThomasOntology Term : 'Alzheimer disease pathway' added !
45167view 22:45, 6 October 2011NsalomonisSpecify description
45166view 22:39, 6 October 2011NsalomonisPeriodical save, work in progress
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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

<cite>No annotated interactions</cite>