Entry
Name
Alzheimer disease
Description
Alzheimer 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. 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. It was proposed that Abeta form Ca2+ permeable pores and bind to and modulate multiple synaptic proteins, including NMDAR, mGluR5 and VGCC, leading to the overfilling of neurons with calcium ions. Consequently, cellular Ca2+ disruptions will lead to neuronal apoptosis, autophagy deficits, mitochondrial abnormality, defective neurotransmission, impaired synaptic plasticity and neurodegeneration in AD. FAD-linked PS1 mutation downregulates the unfolded protein response and leads to vulnerability to ER stress.
Class
Human Diseases; Neurodegenerative disease
BRITE hierarchy
Pathway map
Ortholog table
Disease
Reference
Authors
Dickson DW
Title
Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect?
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Reference
Authors
Takuma K, Yan SS, Stern DM, Yamada K
Title
Mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis in Alzheimer's disease.
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Reference
Authors
Bezprozvanny I, Mattson MP
Title
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
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Reference
Authors
Holscher C
Title
Possible causes of Alzheimer's disease: amyloid fragments, free radicals, and calcium homeostasis.
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Reference
Authors
Bojarski L, Herms J, Kuznicki J
Title
Calcium dysregulation in Alzheimer's disease.
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Reference
Authors
Kondratskyi A, Kondratska K, Skryma R, Prevarskaya N
Title
Ion channels in the regulation of apoptosis.
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Reference
Authors
Popugaeva E, Pchitskaya E, Bezprozvanny I
Title
Dysregulation of Intracellular Calcium Signaling in Alzheimer's Disease.
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Reference
Authors
Tan Y, Deng Y, Qing H
Title
Calcium channel blockers and Alzheimer's disease.
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Reference
Authors
Small DH, Mok SS, Bornstein JC
Title
Alzheimer's disease and Abeta toxicity: from top to bottom.
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Reference
Authors
Parihar MS, Hemnani T
Title
Alzheimer's disease pathogenesis and therapeutic interventions.
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Reference
Authors
Cowburn RF, Popescu BO, Ankarcrona M, Dehvari N, Cedazo-Minguez A
Title
Presenilin-mediated signal transduction.
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Reference
Authors
Honarnejad K, Herms J
Title
Presenilins: role in calcium homeostasis.
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Reference
Authors
Supnet C, Bezprozvanny I
Title
Presenilins function in ER calcium leak and Alzheimer's disease pathogenesis.
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Reference
Authors
Hauptmann S, Keil U, Scherping I, Bonert A, Eckert A, Muller WE
Title
Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease.
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Reference
Authors
Chen Y, Liu W, McPhie DL, Hassinger L, Neve RL
Title
APP-BP1 mediates APP-induced apoptosis and DNA synthesis and is increased in Alzheimer's disease brain.
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Reference
Authors
Eckert A, Nisbet R, Grimm A, Gotz J
Title
March separate, strike together--role of phosphorylated TAU in mitochondrial dysfunction in Alzheimer's disease.
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Reference
Authors
Strickland MR, Holtzman DM
Title
Dr. Jekyll and Mr. Hyde: ApoE explains opposing effects of neuronal LRP1.
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Reference
Authors
Ivins KJ, Thornton PL, Rohn TT, Cotman CW
Title
Neuronal apoptosis induced by beta-amyloid is mediated by caspase-8.
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Reference
Authors
Sushma, Mondal AC
Title
Role of GPCR signaling and calcium dysregulation in Alzheimer's disease.
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Reference
Authors
Sanz-Blasco S, Valero RA, Rodriguez-Crespo I, Villalobos C, Nunez L
Title
Mitochondrial Ca2+ overload underlies Abeta oligomers neurotoxicity providing an unexpected mechanism of neuroprotection by NSAIDs.
Journal
Reference
Authors
Mattson MP
Title
ER calcium and Alzheimer's disease: in a state of flux.
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Reference
Authors
Lee SY, Hwang DY, Kim YK, Lee JW, Shin IC, Oh KW, Lee MK, Lim JS, Yoon DY, Hwang SJ, Hong JT
Title
PS2 mutation increases neuronal cell vulnerability to neurotoxicants through activation of caspase-3 by enhancing of ryanodine receptor-mediated calcium release.
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Reference
Authors
Katayama T, Imaizumi K, Honda A, Yoneda T, Kudo T, Takeda M, Mori K, Rozmahel R, Fraser P, George-Hyslop PS, Tohyama M
Title
Disturbed activation of endoplasmic reticulum stress transducers by familial Alzheimer's disease-linked presenilin-1 mutations.
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Reference
Authors
Lane-Donovan C, Herz J
Title
ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease.
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Reference
Authors
Wasser CR, Herz J
Title
Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses.
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Reference
Authors
Lilja AM, Porras O, Storelli E, Nordberg A, Marutle A
Title
Functional interactions of fibrillar and oligomeric amyloid-beta with alpha7 nicotinic receptors in Alzheimer's disease.
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Reference
Authors
Anastasio TJ
Title
Computational identification of potential multitarget treatments for ameliorating the adverse effects of amyloid-beta on synaptic plasticity.
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Reference
Authors
Vargas LM, Cerpa W, Munoz FJ, Zanlungo S, Alvarez AR
Title
Amyloid-beta oligomers synaptotoxicity: The emerging role of EphA4/c-Abl signaling in Alzheimer's disease.
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Reference
Authors
Tu S, Okamoto S, Lipton SA, Xu H
Title
Oligomeric Abeta-induced synaptic dysfunction in Alzheimer's disease.
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Reference
Authors
Palomer E, Buechler J, Salinas PC
Title
Wnt Signaling Deregulation in the Aging and Alzheimer's Brain.
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Reference
Authors
Vallee A, Lecarpentier Y
Title
Alzheimer Disease: Crosstalk between the Canonical Wnt/Beta-Catenin Pathway and PPARs Alpha and Gamma.
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Reference
Authors
Origlia N, Arancio O, Domenici L, Yan SS
Title
MAPK, beta-amyloid and synaptic dysfunction: the role of RAGE.
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Reference
Authors
Srikanth V, Maczurek A, Phan T, Steele M, Westcott B, Juskiw D, Munch G
Title
Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease.
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Reference
Authors
Pigino G, Morfini G, Pelsman A, Mattson MP, Brady ST, Busciglio J
Title
Alzheimer's presenilin 1 mutations impair kinesin-based axonal transport.
Journal
Reference
Authors
Roy S, Zhang B, Lee VM, Trojanowski JQ
Title
Axonal transport defects: a common theme in neurodegenerative diseases.
Journal
Reference
Authors
Ferreira ST, Lourenco MV, Oliveira MM, De Felice FG
Title
Soluble amyloid-beta oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease.
Journal
Reference
Authors
De Felice FG, Lourenco MV, Ferreira ST
Title
How does brain insulin resistance develop in Alzheimer's disease?
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Reference
Authors
Bedse G, Di Domenico F, Serviddio G, Cassano T
Title
Aberrant insulin signaling in Alzheimer's disease: current knowledge.
Journal
Reference
Authors
Funderburk SF, Marcellino BK, Yue Z
Title
Cell "self-eating" (autophagy) mechanism in Alzheimer's disease.
Journal
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KO pathway