%0 Journal Article
%T The culprit behind amyloid beta peptide related neurotoxicity in Alzheimer's disease: oligomer size or conformation?
%A Kerensa Broersen
%A Frederic Rousseau
%A Joost Schymkowitz
%J Alzheimer's Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/alzrt36
%X The original amyloid cascade hypothesis for Alzheimer's disease (AD) [1] has recently been reformulated to focus on soluble aggregates as the pathogenic molecular form of the amyloid beta peptide (A¦Â) [2] (Figure 1). A¦Â is naturally presentin the brain and cerebrospinal fluid of humans throughout life [3]. Its role is currently unknown. The mere presence of A¦Â in the brain is not sufficient to cause symptoms of neurodegeneration. It has been recognized previously that neuronal injury is rather the result of ordered A¦Â self-association [4]. The amyloid plaques found in AD patient brains, which serve as a hallmark for AD, have been found to contain vast amounts of A¦Â organized into amyloid fibrils. There is no clear correlation, however, between the presence of the A¦Â containing plaques in the brain and the severity of the neurodegenerative symptoms observed in AD patients [5]. Therefore, the focus of research in this area has shifted from senile plaques toward soluble oligomeric conformations of A¦Â as the toxic species as these strongly correlate with the severity of dementia [2,6,7]. This oligomeric form of A¦Â is highly toxic to the brain and is the trigger for loss of synapses and neuronal damage [8,9]. Because of this, many laboratories have been hunting for a specific molecular assembly of defined size that is the main trigger of AD. The result has been the identification of a host of molecular species of A¦Â, ranging from dimers [10-12], trimers [13] and A¦Â species with a molecular weight of 56 kDa [14] to A¦Â-derived diffusible ligands (ADDLs) [15,16] and protofibrils [17] in potent neurotoxic fractions. All are capable of impairing memory formation in mice and their formation and significant accumulation in the brain should thus be considered a potential cause of AD.Recent in vitro studies of the amyloid formation of A¦Â demonstrate that the species mentioned all occur but that they are only transiently populated [18-21]. Moreover, their isolation and characteriz
%U http://alzres.com/content/2/4/12