What is the amyloid cascade hypothesis?
The accumulation of normally soluble beta-amyloid, in particular the A-beta42 peptide, in the brain initiates a cascade of events that promotes its conversion from soluble fibrils to insoluble oligomers that aggregate into fibrous A-beta masses that eventually become amyloid plaques. This amyloid cascade ultimately leads to neuronal dysfunction, neurodegeneration and cell death.[1] The principal component of amyloid is the beta-amyloid protein (A-beta), a 38–43 amino acid peptide formed from the extracellular domain of the amyloid precursor protein (APP). When APP is cleaved by an enzyme, called alpha-secretase, the resulting smaller protein does not develop amyloid plaques. However, g- and beta-secretase enzymes cleave longer forms of beta-amyloid. A-beta40 is by far the most dominant form and is present in everyone as a single monomer. Several genetic mutations appear to influence APP processing and result in the production of higher levels of A-beta or longer A-beta-related peptides
