KEGG   PATHWAY: hsa05010Help
Entry
hsa05010                    Pathway                                

Name
Alzheimer's disease - Homo sapiens (human)
Description
Alzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. The extracellular Abeta oligomers may activate caspases through activation of cell surface death receptors. Alternatively, intracellular Abeta may contribute to pathology by facilitating tau hyper-phosphorylation, disrupting mitochondria function, and triggering calcium dysfunction. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specfically the more amyloidogenic form, Abeta42. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.
Class
Human Diseases; Neurodegenerative diseases
BRITE hierarchy
Pathway map
Alzheimer's disease
hsa05010

All organismsOrtholog table
Disease
H00056  
Alzheimer's disease (AD)
Drug
D03100  
Besonprodil (USAN)
D04905  
Memantine hydrochloride (JAN/USAN)
D08174  
Memantine (INN)
D08869  
Begacestat (USAN/INN)
D09010  
Tarenflurbil (USAN/INN)
D09377  
Semagacestat (USAN/INN)
D09869  
Avagacestat (USAN)
D09917  
Latrepirdine (USAN/INN)
D09918  
Latrepirdine dihydrochloride (USAN)
D10739  
Verubecestat (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
102  
ADAM10; ADAM metallopeptidase domain 10 [KO:K06704] [EC:3.4.24.81]
6868  
ADAM17; ADAM metallopeptidase domain 17 [KO:K06059] [EC:3.4.24.86]
351  
APP; amyloid beta precursor protein [KO:K04520]
8883  
NAE1; NEDD8 activating enzyme E1 subunit 1 [KO:K04532]
322  
APBB1; amyloid beta precursor protein binding family B member 1 [KO:K04529]
2597  
GAPDH; glyceraldehyde-3-phosphate dehydrogenase [KO:K00134] [EC:1.2.1.12]
23621  
BACE1; beta-site APP-cleaving enzyme 1 [KO:K04521] [EC:3.4.23.46]
25825  
BACE2; beta-site APP-cleaving enzyme 2 [KO:K07747] [EC:3.4.23.45]
55851  
PSENEN; presenilin enhancer gamma secretase subunit [KO:K06170]
5663  
PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5664  
PSEN2; presenilin 2 [KO:K04522] [EC:3.4.23.-]
23385  
NCSTN; nicastrin [KO:K06171]
51107  
APH1A; aph-1 homolog A, gamma secretase subunit [KO:K06172]
83464  
APH1B; aph-1 homolog B, gamma secretase subunit [KO:K06172]
3416  
IDE; insulin degrading enzyme [KO:K01408] [EC:3.4.24.56]
4311  
MME; membrane metallo-endopeptidase [KO:K01389] [EC:3.4.24.11]
4723  
NDUFV1; NADH:ubiquinone oxidoreductase core subunit V1 [KO:K03942] [EC:1.6.99.3 1.6.5.3]
4729  
NDUFV2; NADH:ubiquinone oxidoreductase core subunit V2 [KO:K03943] [EC:1.6.99.3 1.6.5.3]
4731  
NDUFV3; NADH:ubiquinone oxidoreductase subunit V3 [KO:K03944]
4694  
NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945]
4695  
NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946]
4696  
NDUFA3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947]
4697  
NDUFA4; NDUFA4, mitochondrial complex associated [KO:K03948]
56901  
NDUFA4L2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948]
4698  
NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949]
4700  
NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950]
4701  
NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951]
4702  
NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952]
4704  
NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953]
4705  
NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954]
4706  
NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955]
126328  
NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956]
55967  
NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352]
51079  
NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353]
4707  
NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957]
4708  
NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958]
4709  
NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959]
4710  
NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960]
4711  
NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961]
4712  
NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962]
4713  
NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963]
4714  
NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964]
4715  
NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965]
4716  
NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966]
54539  
NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351]
4719  
NDUFS1; NADH:ubiquinone oxidoreductase core subunit S1 [KO:K03934] [EC:1.6.99.3 1.6.5.3]
4720  
NDUFS2; NADH:ubiquinone oxidoreductase core subunit S2 [KO:K03935] [EC:1.6.99.3 1.6.5.3]
4722  
NDUFS3; NADH:ubiquinone oxidoreductase core subunit S3 [KO:K03936] [EC:1.6.99.3 1.6.5.3]
4724  
NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937]
4725  
NDUFS5; NADH:ubiquinone oxidoreductase subunit S5 [KO:K03938]
4726  
NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939]
374291  
NDUFS7; NADH:ubiquinone oxidoreductase core subunit S7 [KO:K03940] [EC:1.6.99.3 1.6.5.3]
4728  
NDUFS8; NADH:ubiquinone oxidoreductase core subunit S8 [KO:K03941] [EC:1.6.99.3 1.6.5.3]
4717  
NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967]
4718  
NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968]
NDUFC2-KCTD14; NDUFC2-KCTD14 readthrough [KO:K03968]
6389  
SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234] [EC:1.3.5.1]
6390  
SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235] [EC:1.3.5.1]
6391  
SDHC; succinate dehydrogenase complex subunit C [KO:K00236]
6392  
SDHD; succinate dehydrogenase complex subunit D [KO:K00237]
7386  
UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:1.10.2.2]
4519  
CYTB; cytochrome b [KO:K00412]
1537  
CYC1; cytochrome c1 [KO:K00413]
7384  
UQCRC1; ubiquinol-cytochrome c reductase core protein I [KO:K00414]
7385  
UQCRC2; ubiquinol-cytochrome c reductase core protein II [KO:K00415]
7388  
UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
440567  
UQCRHL; ubiquinol-cytochrome c reductase hinge protein like [KO:K00416]
7381  
UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
27089  
UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII [KO:K00418]
29796  
UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
10975  
UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
4514  
COX3; cytochrome c oxidase III [KO:K02262]
4512  
COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:1.9.3.1]
4513  
COX2; cytochrome c oxidase subunit II [KO:K02261]
84701  
COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263]
1327  
COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263]
9377  
COX5A; cytochrome c oxidase subunit 5A [KO:K02264]
1329  
COX5B; cytochrome c oxidase subunit 5B [KO:K02265]
1337  
COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266]
1339  
COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266]
1340  
COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267]
125965  
COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
1345  
COX6C; cytochrome c oxidase subunit 6C [KO:K02268]
1346  
COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270]
1347  
COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270]
9167  
COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270]
1349  
COX7B; cytochrome c oxidase subunit 7B [KO:K02271]
170712  
COX7B2; cytochrome c oxidase subunit 7B2 [KO:K02271]
1350  
COX7C; cytochrome c oxidase subunit 7C [KO:K02272]
341947  
COX8C; cytochrome c oxidase subunit 8C [KO:K02273]
1351  
COX8A; cytochrome c oxidase subunit 8A [KO:K02273]
498  
ATP5A1; ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle [KO:K02132]
506  
ATP5B; ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide [KO:K02133] [EC:3.6.3.14]
509  
ATP5C1; ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 [KO:K02136]
513  
ATP5D; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134]
514  
ATP5E; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135]
4508  
ATP6; ATP synthase F0 subunit 6 [KO:K02126]
515  
ATP5F1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit B1 [KO:K02127]
516  
ATP5G1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C1 (subunit 9) [KO:K02128]
517  
ATP5G2; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C2 (subunit 9) [KO:K02128]
518  
ATP5G3; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C3 (subunit 9) [KO:K02128]
10476  
ATP5H; ATP synthase, H+ transporting, mitochondrial Fo complex subunit D [KO:K02138]
539  
ATP5O; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137]
522  
ATP5J; ATP synthase, H+ transporting, mitochondrial Fo complex subunit F6 [KO:K02131]
4509  
ATP8; ATP synthase F0 subunit 8 [KO:K02125]
3028  
HSD17B10; hydroxysteroid (17-beta) dehydrogenase 10 [KO:K08683] [EC:1.1.1.178 1.1.1.35]
4023  
LPL; lipoprotein lipase [KO:K01059] [EC:3.1.1.34]
348  
APOE; apolipoprotein E [KO:K04524]
4035  
LRP1; LDL receptor related protein 1 [KO:K04550]
355  
FAS; Fas cell surface death receptor [KO:K04390]
7132  
TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
8772  
FADD; Fas associated via death domain [KO:K02373]
841  
CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
637  
BID; BH3 interacting domain death agonist [KO:K04726]
810  
CALML3; calmodulin like 3 [KO:K02183]
805  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin like 6 [KO:K02183]
51806  
CALML5; calmodulin like 5 [KO:K02183]
5530  
PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268]
572  
BAD; BCL2 associated agonist of cell death [KO:K02158]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
317  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
836  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
2776  
GNAQ; G protein subunit alpha q [KO:K04634]
23236  
PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
2902  
GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208]
2903  
GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209]
2904  
GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]
2905  
GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211]
2906  
GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212]
775  
CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
776  
CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
778  
CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
779  
CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6263  
RYR3; ryanodine receptor 3 [KO:K04963]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960]
487  
ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:3.6.3.8]
489  
ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:3.6.3.8]
488  
ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:3.6.3.8]
22926  
ATF6; activating transcription factor 6 [KO:K09054]
2081  
ERN1; endoplasmic reticulum to nucleus signaling 1 [KO:K08852] [EC:3.1.26.- 2.7.11.1]
9451  
EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 [KO:K08860] [EC:2.7.11.1]
CASP12; caspase 12 (gene/pseudogene) [KO:K04741] [EC:3.4.22.-]
4842  
NOS1; nitric oxide synthase 1 [KO:K13240] [EC:1.14.13.39]
823  
CAPN1; calpain 1 [KO:K01367] [EC:3.4.22.52]
824  
CAPN2; calpain 2 [KO:K03853] [EC:3.4.22.53]
8851  
CDK5R1; cyclin-dependent kinase 5, regulatory subunit 1 (p35) [KO:K11716]
1020  
CDK5; cyclin-dependent kinase 5 [KO:K02090] [EC:2.7.11.22]
4137  
MAPT; microtubule associated protein tau [KO:K04380]
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
840  
CASP7; caspase 7 [KO:K04397] [EC:3.4.22.60]
6622  
SNCA; synuclein alpha [KO:K04528]
7124  
TNF; tumor necrosis factor [KO:K03156]
3553  
IL1B; interleukin 1 beta [KO:K04519]
Compound
C00027  
Hydrogen peroxide
C00070  
Copper
C00076  
Calcium cation
C00533  
Nitric oxide
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C14818  
Fe2+
C16845  
Peroxynitrite
Reference
  Authors
Dickson DW
  Title
Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
  Journal
J Clin Invest 114:23-7 (2004)
Reference
  Authors
Takuma K, Yan SS, Stern DM, Yamada K
  Title
Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.
  Journal
J Pharmacol Sci 97:312-6 (2005)
Reference
  Authors
Bezprozvanny I, Mattson MP
  Title
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
  Journal
Trends Neurosci 31:454-63 (2008)
Reference
PMID:9848086
  Authors
Holscher C
  Title
Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis.
  Journal
Neurobiol Dis 5:129-41 (1998)
Reference
  Authors
Bojarski L, Herms J, Kuznicki J
  Title
Calcium dysregulation in Alzheimer's disease.
  Journal
Neurochem Int 52:621-33 (2008)
Reference
  Authors
Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M
  Title
Induction of neuronal death by ER stress in Alzheimer's disease.
  Journal
J Chem Neuroanat 28:67-78 (2004)
Reference
  Authors
Small DH, Mok SS, Bornstein JC
  Title
Alzheimer's disease and Abeta toxicity: from top to bottom.
  Journal
Nat Rev Neurosci 2:595-8 (2001)
Reference
  Authors
Mattson MP
  Title
Pathways towards and away from Alzheimer's disease.
  Journal
Nature 430:631-9 (2004)
Reference
  Authors
Parihar MS, Hemnani T
  Title
Alzheimer's disease pathogenesis and therapeutic interventions.
  Journal
J Clin Neurosci 11:456-67 (2004)
Reference
  Authors
Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A
  Title
Presenilin-mediated signal transduction.
  Journal
Physiol Behav 92:93-7 (2007)
Reference
  Authors
Shen Y, He P, Zhong Z, McAllister C, Lindholm K
  Title
Distinct destructive signal pathways of neuronal death in Alzheimer's disease.
  Journal
Trends Mol Med 12:574-9 (2006)
Reference
  Authors
Reese LC, Zhang W, Dineley KT, Kayed R, Taglialatela G
  Title
Selective induction of calcineurin activity and signaling by oligomeric amyloid beta.
  Journal
Aging Cell 7:824-35 (2008)
Reference
  Authors
Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH
  Title
Neurotoxicity induces cleavage of p35 to p25 by calpain.
  Journal
Nature 405:360-4 (2000)
Reference
  Authors
Hauptmann S, Keil U, Scherping I, Bonert A, Eckert A, Muller WE
  Title
Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease.
  Journal
Exp Gerontol 41:668-73 (2006)
Reference
  Authors
Avila J
  Title
Tau phosphorylation and aggregation in Alzheimer's disease pathology.
  Journal
FEBS Lett 580:2922-7 (2006)
Reference
  Authors
Ivins KJ, Thornton PL, Rohn TT, Cotman CW
  Title
Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.
  Journal
Neurobiol Dis 6:440-9 (1999)
Reference
  Authors
Gandy S
  Title
The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease.
  Journal
J Clin Invest 115:1121-9 (2005)
KO pathway
 

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