Question

Share your thoughts about why is amyloid toxic to cells and how does it contribute to neurodegenerative disorders, such as Alzheimer's disease. (Cite any sources used, minimum 8 sentences)

Answer 1

The mechanism by which amyloid beta may damage and kill neurons is by generating reactive oxygen species during the process of its self-aggregation. When this occurs on the membrane of neurons it causes lipid peroxidation and the generation of a toxic aldehyde called 4-hydroxynonenal which, in turn, impairs the function of ion-motive ATPases, glucose transporters and glutamate transporters. As a result, amyloid beta promotes depolarization of the synaptic membrane, excessive calcium influx and mitochondrial impairment

Amyloid beta (Aβ) is a peptide of 39–43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer’s disease. For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia.

One of these hypotheses is the “amyloid hypothesis,” which supports the idea that beta-amyloid peptide (Aβ) plays a very important role in the origin and progression of the nervous tissue damage seen in these patients. Some evidences support this hypothesis:

(1) the demonstration of Aβ as the principal component of both the neuritic plaques and the amyloid angiopathy observed in the Alzheimer’s patients.

(2) the observations in which mutations responsible for familial forms of AD drive in some way an increase in the Aβ production.

(3) the several toxic effects that Aβ has shown both at in vitro as in vivo experiments, which reproduce some of the observed alterations in Alzheimer’s disease, Such evidences suggest that either an excessive production of Aβ or impairment in its adequate clearance could be the key events in the origin and progression of the neuronal damage.