A modified beta-amyloid hypothesis: intraneuronal accumulation of the beta-amyloid peptide--the first step of a fatal cascade.
Accumulating evidence points to an important role of intraneuronal A beta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. In the present article, we review recent findings on intracellular monomeric and oligomeric beta-amyloid (A beta) generation and its pathological function in cell culture, transgenic AD mouse models and post mortem brain tissue of AD and Down syndrome patients, as well as its interaction with oxidative stress and its relevance in apoptotic cell death. Based on these results, a modified A beta hypothesis is formulated, that integrates biochemical, neuropathological and genetic observations with AD-typical neuron loss and plaque formation.
Saarland University, Department of Psychiatry, Division of Neurobiology, 66421 Homburg/Saar, Germany. oliver.wirths@uniklinik-saarland.de
Oliver
O
Wirths
Gerd
G
Multhaup
Thomas A
TA
Bayer
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D018450:Disease Progression; D004314:Down Syndrome / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress
D016229:Amyloid beta-Peptides