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. 2006 Apr 5;11(1):1–11. doi: 10.1111/j.1750-3639.2001.tb00376.x

Key Factors in Alzheimer's Disease: β‐amyloid Precursor Protein Processing, Metabolism and Intraneuronal Transport

Thomas A Bayer 1,✉, Oliver Wirths 1, Katalin Majtényi 2, Tobias Hartmann 3, Gerd Multhaup 3, Konrad Beyreuther 3, Christian Czech 4,4
PMCID: PMC8098450  PMID: 11145195

Abstract

During the last years it has become evident that the β‐amyloid (Aβ) component of senile plaques may be the key molecule in the pathology of Alzheimer's disease (AD). The source and place of the neurotoxic action of Aβ, however, is still a matter of controversy. The precursor of the β‐amyloid peptide is the predominantly neuronal β‐amyloid precursor protein. We, and others, hypothesize that intraneuronal misregulation of APP leads to an accumulation of Aβ peptides in intracellular compartments. This accumulation impairs APP trafficking, which starts a cascade of pathological changes and causes the pyramidal neurons to degenerate. Enhanced Aβ secretion as a function of stressed neurons and remnants of degenerated neurons provide seeds for extracellular Aβ aggregates, which induce secondary degenerative events involving neighboring cells such as neurons, astroglia and macrophages/microglia.

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