Background: Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by αand γ-secretases, to form the nonpathogenic sAPPα and p3 fragments. By contrast, amyloid-beta (Aβ) is produced via proteolytic cleavage by βand γ-secretases. In Alzheimer’s disease (AD), APP is preferentially processed via the amyloidogenic pathway, producing large amounts of Aβ that...

BACKGROUND Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by α- and γ-secretases, to form the nonpathogenic sAPPα and p3 fragments. By contrast, amyloid-beta (Aβ) is produced via proteolytic cleavage by β- and γ-secretases. In Alzheimer's disease (AD), APP is preferentially processed via the amyloidogenic pathway, producing large amounts of Aβ t...

Intracellular trafficking and proteolytic processing of amyloid precursor protein (APP) have been the focus of numerous investigations over the past two decades. APP is the precursor to the amyloid beta-protein (Abeta), the 38-43-amino acid residue peptide that is at the heart of the amyloid cascade hypothesis of Alzheimer disease (AD). Tremendous progress has been made since the initial identi...

The possibility to understand the causes and treat the symptoms of Alzheimer's disease patients is still a great challenge. The triggering events leading to the selective neurodegeneration observed in Alzheimer's brains are not completely understood. This lack of understanding of the pathophysiological processes posses an important theoretical challenge for the rational design of pharmacologica...

Alzheimer's disease (AD), the leading cause of dementia worldwide, is characterized by the accumulation of the β-amyloid peptide (Aβ) within the brain along with hyperphosphorylated and cleaved forms of the microtubule-associated protein tau. Genetic, biochemical, and behavioral research suggest that physiologic generation of the neurotoxic Aβ peptide from sequential amyloid precursor protein (...

Cerebral deposition of beta-amyloid protein is a pathological feature central to Alzheimer's disease. Production of beta-amyloid by proteolytic processing of the beta-amyloid precursor protein (beta APP) is a critical initial step in beta-amyloidogenesis. We use an inhibitor of beta APP processing to block beta-amyloid peptide formation. Application of the inhibitor to cultured cells results in...