title: Always around, never the same: pathways of amyloid beta induced neurodegeneration throughout the pathogenic cascade of Alzheimer's disease.
abstract: There is an increasing amount of evidence showing the importance of intermediate aggregation species of amyloid beta (Abeta) in the pathogenic cascade of Alzheimer's disease (AD). Different Abeta assembly forms may mediate diverse toxic effects at different stages of the disease. Mouse models for AD suggest that intraneuronal accumulation of Abeta oligomers might be involved in AD pathogenesis at a very early stage of the disease. The detrimental effect of oligomeric Abeta on synaptic efficacy is suggested to be an early event in the pathogenic cascade. Also early neuronal responses as activation of the unfolded protein response are processes likely to be associated with the increased occurrence of oligomeric or low fibrillar Abeta in AD pathology. In later stages of AD pathology, the fibrillarity of Abeta increases, concomitantly with a neuroinflammatory response, followed by tau related neurofibrillary changes in end stage pathology. We will review recent findings in in vitro cell models, in vivo mouse models, and post mortem AD brain tissue in view of the effects of different Abeta peptide species on neurodegeneration during AD pathogenesis. Insight into the role of different Abeta species during AD pathogenesis is essential for the development of disease modifying drugs and therapeutical strategies.
authors.affiliation: Academic Medical Center, Neurogenetics Laboratory, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: J J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.forename: S M
authors.initials: SM
authors.lastname: Chafekar
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: P
authors.initials: P
authors.lastname: Eikelenboom
authors.forename: W
authors.initials: W
authors.lastname: Scheper
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism*; D017510:Protein Folding
chemical_list: D016229:Amyloid beta-Peptides