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The role of the beta-amyloid peptide in Alzheimer's disease - Mechanisms of toxicity

Jansen, S.R. (2009) The role of the beta-amyloid peptide in Alzheimer's disease - Mechanisms of toxicity. Bachelor's Thesis, Biology.

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It is generally believed that the amyloid-β peptide plays a central causative role in the pathogenesis of AD. Aβ is present in the brain is several different aggregation forms, ranging from monomers, soluble oligomers to large insoluble fibrillar species. It was first hypothized that the fibrillar species, which are found mainly in extracellular deposits called plaques, are responsible for the neurotoxic effects observed in AD. More recently more attention has been focused on the role of the soluble oligomeric species. However, the question how Aβ induces the toxic events associated with AD and which species are responsible still remains to be solved. Very striking in AD pathogenesis are synaptic signaling impairments and loss of synapses, which shows good correlation with oligomer levels. Aβ induces these synaptic dysfunctions by altering NMDA and AMPA receptor currents by changing activity of several phosphatases and kinases, resulting in deficiencies in LTP and LTD. Further, there are many indications suggestion a role for oxidative stress in association with Aβ peptides. The increased cellular stress results in increased activation of stress proteins and may eventually result in neuronal death. There is also evidence suggesting a role for NGF and its receptors in Aβ induced neuropathology. Results from studies considering the role of Wnt signaling suggest that wnt signaling might be impaired in AD and that its loss of function might be crucial in triggering the neurodegenerative processes induced by Aβ peptides. There is also some evidence which suggests that AD is linked to a state of relative brain insulin resistance, mediated by Aβ. Moreover, addition of Aβ causes failure in several components involved in calcium homeostasis, leading to calcium homeostasis impairments. Further, it has been indicated that Aβ induced mitochondrial failure could be an early event in the pathogenesis of AD. Considering the role of Aβ in cholinergic dysfunction, it has been stated that ACh release and synthesis are depressed and ACh degradation is affected in the presence of Aβ peptides. There is also a large body of evidence supporting the notion that AD is associated with a chronic upregulation of inflammatory responses, induced by Aβ. AD is characterized by progressive loss of neurons, and several mechanisms have been described in which Aβ could lead to apoptosis.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:28
Last Modified: 15 Feb 2018 07:28

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