Affiliations: [a] The Florey Institute of Neuroscience and Mental Health, Division of Mental Health, Parkville, VIC, Australia | [b] The Department of Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC, Australia
Correspondence:
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Correspondence to: David Finkelstein or Paul Adlard, The Florey Institute of Neuroscience and Mental Health, Level 4 Kenneth Myer Building, 30 Royal Parade, Parkville, VIC 3052, Australia. Tel.: +61 3 90356680 (DF); 90356775 (PA); E-mails: [email protected]; [email protected].
Note: [1] Co-senior authors.
Abstract: Oligomeric forms of amyloid-β (Aβ) are thought to be responsible for the pathogenesis of Alzheimer's disease. While many oligomers of Aβ are thought to be naturally occurring in the brain of humans and/or transgenic animals, it is well known that Aβ oligomers are also readily produced in vitro in the laboratory. In recent studies, we discovered that synthetic monomeric Aβ (4.7 kDa) could be transformed by microdialysis to higher molecular weight species (approximately 56 kDa, by western blot). Surface-enhanced laser desorption/ionization mass spectrometry and electron microscopy further identified these species' as potential Aβ oligomers. The production of similar species could also be produced by centrifugal filtration and this formation was concentration and pore-size dependent. These higher order species of Aβ were resistant to dissolution in NaOH, HFIP, formic acid, urea, and guanidine. We postulate that we have identified a novel way of producing a high order species of oligomeric Aβ and we provide evidence to suggest that Aβ oligomers can quite easily be a product of normal laboratory practices. These data suggest that the experimental detection of higher order oligomers in tissues derived from Alzheimer's disease brains or from animal models of disease could, in some cases, be a product the method of analysis.
