title: Key factors in Alzheimer's disease: beta-amyloid precursor protein processing, metabolism and intraneuronal transport.
abstract: During the last years it has become evident that the beta-amyloid (Abeta) 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 Abeta, however, is still a matter of controversy. The precursor of the beta-amyloid peptide is the predominantly neuronal beta-amyloid precursor protein. We, and others, hypothesize that intraneuronal misregulation of APP leads to an accumulation of Abeta peptides in intracellular compartments. This accumulation impairs APP trafficking, which starts a cascade of pathological changes and causes the pyramidal neurons to degenerate. Enhanced Abeta secretion as a function of stressed neurons and remnants of degenerated neurons provide seeds for extracellular Abeta aggregates, which induce secondary degenerative events involving neighboring cells such as neurons, astroglia and macrophages/microglia. Beta-amyloid precursor protein has a pivotal role in Alzheimer's disease.
authors.affiliation: Department of Psychiatry, University of Bonn Medical Center, Germany. bayer@uni-bonn.de
authors.forename: T A
authors.initials: TA
authors.lastname: Bayer
authors.forename: O
authors.initials: O
authors.lastname: Wirths
authors.forename: K
authors.initials: K
authors.lastname: Majtényi
authors.forename: T
authors.initials: T
authors.lastname: Hartmann
authors.forename: G
authors.initials: G
authors.lastname: Multhaup
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: C
authors.initials: C
authors.lastname: Czech
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001370:Axonal Transport; D003300:Copper; D006801:Humans; D009473:Neuronal Plasticity; D009435:Synaptic Transmission
chemical_list: D016564:Amyloid beta-Protein Precursor; D003300:Copper