Abstract
The Contribution of the Amyloid Hypothesis to the Understanding of Alzheimer's Disease: A Critical Overview
Highlights
APP Intra Cellular Domain (AICD) gained relevance in the field appears to be a multifunctional factor affecting several physiological processes likely to contribute to Alzheimer’s disease pathology by acting as a transcription factor that controls the expression of a series of proteins involved in control of cell death and Aβ degradation
Aβ peptides are generated in the amyloidogenic pathway of APP processing by sequential proteolysis by β- and γ-secretases
The steady state of monomeric Aβ in the brain is the result of a tightly controlled balance between production and removal; sporadic Alzheimer’s disease (AD) may reflect defects in clearance mechanisms for Aβ rather than in the enhanced synthesis which occurs in early-onset cases
Summary
APP Intra Cellular Domain (AICD) gained relevance in the field appears to be a multifunctional factor affecting several physiological processes likely to contribute to Alzheimer’s disease pathology by acting as a transcription factor that controls the expression of a series of proteins involved in control of cell death and Aβ degradation. Aβ peptides are generated in the amyloidogenic pathway of APP processing by sequential proteolysis by β- and γ-secretases. In the alternative nonamyloidogenic APP processing pathway, α-secretase cleaves within the Aβ peptide region and prevents Aβ generation.
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