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A modified β‐amyloid hypothesis: intraneuronal accumulation of the β‐amyloid peptide – the first step of a fatal cascade
Author(s) -
Wirths Oliver,
Multhaup Gerd,
Bayer Thomas A.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02737.x
Subject(s) - neurodegeneration , neuroscience , intracellular , pathological , amyloid (mycology) , oxidative stress , transgene , programmed cell death , loss function , genetically modified mouse , alzheimer's disease , disease , apoptosis , biology , pathology , microbiology and biotechnology , medicine , endocrinology , biochemistry , gene , phenotype
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.