Amyloid Beta Research Paper

In order to understand the hypothesis, first we must understand what is amyloid-beta, and how it is synthesized. Amyloid-beta is a peptide cleaved from the amyloid-beta precursor protein, which is a larger integral membrane protein found concentrated in neuronal synapsis (Masters et al., 1985;Glenner & Wong, 1984). An existing mutation in APP would lead to an increased cleavage and to a different availability of its sub products, hence increasing the amount of amyloid-beta being synthesized. A mutation in the chromosome 21, which also carriers the APP gene, leads to accumulation of plaques and tangles, as observer in patients with Down syndrome (Tanzi et al., 1991). The amyloid-beta protein is composed of both hydrophobic and hydrophilic ends, this amphipathic characteristic allows the peptide to auto-aggregate and form fibrils in order to hide its hydrophobic extremity (Giuseppe et al., 2003). Aβ40 and Aβ42 are the two main types of amyloid-beta. The second one has a higher accumulation and polymerizing ability therefore is considered to be the more pathological of the two and is found within neuritic plaques (Lippa et al., 1998). However Aβ42 only accounts for 10% of the total Aβ being released by neuronal tissues (Giuseppe et al., 2003). Aβ40, which can be found …show more content…
After the first Aβ deposits it has the ability to physically stimulate further deposition of other Aβ peptides, leading to additional reorganization and formation of neuritic plaques. According to Cummings et al., once the plaques are mature they are able to activate the neighboring tissue, including microglia and astrocytes, culminating in neuronal damage and synaptic dysfunction. This pathological scenario is thought to be a result of oxidative injury and phosphorylation linked to the presence of the plaques as well as the accumulation of the tau tangles (Lamberts et al.,