KEGG   PATHWAY: ko05010Help
Entry
ko05010                     Pathway                                
Name
Alzheimer's disease
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
ko05010

All organismsOrtholog table
Disease
H00056  
Alzheimer's disease (AD)
H00473  
Mitochondrial respiratory chain deficiencies (MRCD)
Orthology
K06704  
disintegrin and metalloproteinase domain-containing protein 10 [EC:3.4.24.81]
K06059  
disintegrin and metalloproteinase domain-containing protein 17 [EC:3.4.24.86]
K04520  
amyloid beta A4 protein
K04532  
amyloid beta precursor protein binding protein 1
K04529  
amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65)
K00134  
glyceraldehyde 3-phosphate dehydrogenase [EC:1.2.1.12]
K04521  
beta-site APP-cleaving enzyme 1 (memapsin 2) [EC:3.4.23.46]
K07747  
beta-site APP-cleaving enzyme 2 (memapsin 1) [EC:3.4.23.45]
K06170  
presenilin enhancer 2
K04505  
presenilin 1 [EC:3.4.23.-]
K04522  
presenilin 2 [EC:3.4.23.-]
K06171  
nicastrin
K06172  
anterior pharynx defective 1
K01408  
insulysin [EC:3.4.24.56]
K01389  
neprilysin [EC:3.4.24.11]
K03942  
NADH dehydrogenase (ubiquinone) flavoprotein 1 [EC:1.6.99.3 1.6.5.3]
K03943  
NADH dehydrogenase (ubiquinone) flavoprotein 2 [EC:1.6.99.3 1.6.5.3]
K03944  
NADH dehydrogenase (ubiquinone) flavoprotein 3 [EC:1.6.99.3 1.6.5.3]
K03945  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 1 [EC:1.6.99.3 1.6.5.3]
K03946  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 2 [EC:1.6.99.3 1.6.5.3]
K03947  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 3 [EC:1.6.99.3 1.6.5.3]
K03948  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 [EC:1.6.99.3 1.6.5.3]
K03949  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 5 [EC:1.6.99.3 1.6.5.3]
K03950  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 6 [EC:1.6.99.3 1.6.5.3]
K03951  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7 [EC:1.6.99.3 1.6.5.3]
K03952  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 8 [EC:1.6.99.3 1.6.5.3]
K03953  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 9 [EC:1.6.99.3 1.6.5.3]
K03954  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 10 [EC:1.6.99.3 1.6.5.3]
K03955  
NADH dehydrogenase (ubiquinone) 1 alpha/beta subcomplex 1 [EC:1.6.99.3 1.6.5.3]
K03956  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 11 [EC:1.6.5.3]
K11352  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 12 [EC:1.6.99.3 1.6.5.3]
K11353  
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 13 [EC:1.6.99.3 1.6.5.3]
K03957  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 1 [EC:1.6.99.3 1.6.5.3]
K03958  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 2 [EC:1.6.99.3 1.6.5.3]
K03959  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 3 [EC:1.6.99.3 1.6.5.3]
K03960  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 4 [EC:1.6.99.3 1.6.5.3]
K03961  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 5 [EC:1.6.99.3 1.6.5.3]
K03962  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 6 [EC:1.6.99.3 1.6.5.3]
K03963  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 7 [EC:1.6.99.3 1.6.5.3]
K03964  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 [EC:1.6.99.3 1.6.5.3]
K03965  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 9 [EC:1.6.99.3 1.6.5.3]
K03966  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 10 [EC:1.6.99.3 1.6.5.3]
K11351  
NADH dehydrogenase (ubiquinone) 1 beta subcomplex 11 [EC:1.6.99.3 1.6.5.3]
K03934  
NADH dehydrogenase (ubiquinone) Fe-S protein 1 [EC:1.6.99.3 1.6.5.3]
K03935  
NADH dehydrogenase (ubiquinone) Fe-S protein 2 [EC:1.6.99.3 1.6.5.3]
K03936  
NADH dehydrogenase (ubiquinone) Fe-S protein 3 [EC:1.6.99.3 1.6.5.3]
K03937  
NADH dehydrogenase (ubiquinone) Fe-S protein 4 [EC:1.6.99.3 1.6.5.3]
K03938  
NADH dehydrogenase (ubiquinone) Fe-S protein 5 [EC:1.6.99.3 1.6.5.3]
K03939  
NADH dehydrogenase (ubiquinone) Fe-S protein 6 [EC:1.6.99.3 1.6.5.3]
K03940  
NADH dehydrogenase (ubiquinone) Fe-S protein 7 [EC:1.6.99.3 1.6.5.3]
K03941  
NADH dehydrogenase (ubiquinone) Fe-S protein 8 [EC:1.6.99.3 1.6.5.3]
K03967  
NADH dehydrogenase (ubiquinone) 1 subcomplex unknown 1 [EC:1.6.99.3 1.6.5.3]
K03968  
NADH dehydrogenase (ubiquinone) 1 subcomplex unknown 2 [EC:1.6.99.3 1.6.5.3]
K00234  
succinate dehydrogenase (ubiquinone) flavoprotein subunit [EC:1.3.5.1]
K00235  
succinate dehydrogenase (ubiquinone) iron-sulfur subunit [EC:1.3.5.1]
K00236  
succinate dehydrogenase (ubiquinone) cytochrome b560 subunit
K00237  
succinate dehydrogenase (ubiquinone) membrane anchor subunit
K00411  
ubiquinol-cytochrome c reductase iron-sulfur subunit [EC:1.10.2.2]
K00412  
ubiquinol-cytochrome c reductase cytochrome b subunit
K00413  
ubiquinol-cytochrome c reductase cytochrome c1 subunit
K00414  
ubiquinol-cytochrome c reductase core subunit 1
K00415  
ubiquinol-cytochrome c reductase core subunit 2
K00416  
ubiquinol-cytochrome c reductase subunit 6
K00417  
ubiquinol-cytochrome c reductase subunit 7
K00418  
ubiquinol-cytochrome c reductase subunit 8
K00419  
ubiquinol-cytochrome c reductase subunit 9
K00420  
ubiquinol-cytochrome c reductase subunit 10
K02262  
cytochrome c oxidase subunit 3
K02256  
cytochrome c oxidase subunit 1 [EC:1.9.3.1]
K02261  
cytochrome c oxidase subunit 2
K02263  
cytochrome c oxidase subunit 4
K02264  
cytochrome c oxidase subunit 5a
K02265  
cytochrome c oxidase subunit 5b
K02266  
cytochrome c oxidase subunit 6a
K02267  
cytochrome c oxidase subunit 6b
K02268  
cytochrome c oxidase subunit 6c
K02270  
cytochrome c oxidase subunit 7a
K02271  
cytochrome c oxidase subunit 7b
K02272  
cytochrome c oxidase subunit 7c
K02273  
cytochrome c oxidase subunit 8
K02132  
F-type H+-transporting ATPase subunit alpha [EC:3.6.3.14]
K02133  
F-type H+-transporting ATPase subunit beta [EC:3.6.3.14]
K02136  
F-type H+-transporting ATPase subunit gamma [EC:3.6.3.14]
K02134  
F-type H+-transporting ATPase subunit delta [EC:3.6.3.14]
K02135  
F-type H+-transporting ATPase subunit epsilon [EC:3.6.3.14]
K02126  
F-type H+-transporting ATPase subunit a [EC:3.6.3.14]
K02127  
F-type H+-transporting ATPase subunit b [EC:3.6.3.14]
K02128  
F-type H+-transporting ATPase subunit c [EC:3.6.3.14]
K02138  
F-type H+-transporting ATPase subunit d [EC:3.6.3.14]
K02137  
F-type H+-transporting ATPase oligomycin sensitivity conferral protein [EC:3.6.3.14]
K02131  
F-type H+-transporting ATPase subunit 6 [EC:3.6.3.14]
K02125  
F-type H+-transporting ATPase subunit 8 [EC:3.6.3.14]
K08683  
3-hydroxyacyl-CoA dehydrogenase / 3-hydroxy-2-methylbutyryl-CoA dehydrogenase [EC:1.1.1.178 1.1.1.35]
K01059  
lipoprotein lipase [EC:3.1.1.34]
K04524  
apolipoprotein E
K04550  
low-density lipoprotein receptor-related protein 1 (alpha-2-macroglobulin receptor)
K04390  
tumor necrosis factor receptor superfamily member 6
K03158  
tumor necrosis factor receptor superfamily member 1A
K02373  
FAS-associated death domain protein
K04398  
caspase 8 [EC:3.4.22.61]
K04726  
BH3 interacting domain death agonist
K02183  
calmodulin
K04348  
protein phosphatase 3, catalytic subunit [EC:3.1.3.16]
K06268  
protein phosphatase 3, regulatory subunit
K02158  
BCL2-antagonist of cell death
K08738  
cytochrome c
K02084  
apoptotic protease-activating factor
K04399  
caspase 9 [EC:3.4.22.62]
K02187  
caspase 3 [EC:3.4.22.56]
K04634  
guanine nucleotide-binding protein G(q) subunit alpha
K05858  
phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K05208  
glutamate receptor ionotropic, NMDA 1
K05209  
glutamate receptor ionotropic, NMDA 2A
K05210  
glutamate receptor ionotropic, NMDA 2B
K05211  
glutamate receptor ionotropic, NMDA 2C
K05212  
glutamate receptor ionotropic, NMDA 2D
K04850  
voltage-dependent calcium channel L type alpha-1C
K04851  
voltage-dependent calcium channel L type alpha-1D
K04853  
voltage-dependent calcium channel L type alpha-1F
K04857  
voltage-dependent calcium channel L type alpha-1S
K04371  
extracellular signal-regulated kinase 1/2 [EC:2.7.11.24]
K04963  
ryanodine receptor 3
K04958  
inositol 1,4,5-triphosphate receptor type 1
K04959  
inositol 1,4,5-triphosphate receptor type 2
K04960  
inositol 1,4,5-triphosphate receptor type 3
K05853  
Ca2+ transporting ATPase, sarcoplasmic/endoplasmic reticulum [EC:3.6.3.8]
K09054  
cyclic AMP-dependent transcription factor ATF-6 alpha
K08852  
serine/threonine-protein kinase/endoribonuclease IRE1 [EC:3.1.26.- 2.7.11.1]
K08860  
eukaryotic translation initiation factor 2-alpha kinase 3 [EC:2.7.11.1]
K04741  
caspase 12 [EC:3.4.22.-]
K13240  
nitric-oxide synthase, brain [EC:1.14.13.39]
K01367  
calpain-1 [EC:3.4.22.52]
K03853  
calpain-2 [EC:3.4.22.53]
K11716  
cyclin-dependent kinase 5 activator 1
K02090  
cyclin-dependent kinase 5 [EC:2.7.11.22]
K04380  
microtubule-associated protein tau
K03083  
glycogen synthase kinase 3 beta [EC:2.7.11.26]
K04397  
caspase 7 [EC:3.4.22.60]
K04528  
synuclein, alpha (non A4 component of amyloid precursor)
K03156  
tumor necrosis factor superfamily, member 2
K04519  
interleukin 1 beta
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)
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