A modified β-amyloid hypothesis: intraneuronal accumulation of the β-amyloid peptide – the first step of a fatal cascade

Authors


Address correspondence and reprint requests to O. Wirths, Department of Psychiatry, Division of Neurobiology, University of the Saarland Medical Center, Building 90, 66421 Homburg/Saar, Germany.
E-mail: oliver.wirths@uniklinik-saarland.de

Abstract

Accumulating evidence points to an important role of intraneuronal Aβ 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 β-amyloid (Aβ) 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 Aβ hypothesis is formulated, that integrates biochemical, neuropathological and genetic observations with AD-typical neuron loss and plaque formation.

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