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map05010                    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
map05010

All organismsOrtholog table
Disease
H00056  
Alzheimer's disease (AD)
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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