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P1–124: Particular types of beta‐amyloid oligomers are formed in Alzheimer's disease‐like physiopathological conditions
Author(s) -
Ly Myriam,
Delatour Benoît
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.346
Subject(s) - monomer , oligomer , chemistry , in vitro , in vivo , extracellular , blot , amyloid (mycology) , biochemistry , denaturation (fissile materials) , antibody , alzheimer's disease , biophysics , biology , polymer , disease , immunology , medicine , pathology , inorganic chemistry , microbiology and biotechnology , organic chemistry , nuclear chemistry , gene
Background: A b oligomers are today considered as major neurotoxins involved in the pathogenesis of Alzheimer’s disease. These soluble forms of aggregated A b are sensitive to denaturation techniques used in most biochemistry protocols. Here we decided to analyse A b peptides derived from mice brain homogenates, synthetic preparations of "monomeric" A b 1-42 and from ADDls preparations in order to characterize and compare the nature of the oligomers present in these samples. Methods: In order to preserve the nature of oligomers formed, electrophoresis followed by western blotting were performed in non denaturating conditions. Nu1 antibody, specific of oligomeric configurations of A b was used in comparison of commonly used anti-A b (4G8, 6F3D, 6E10, FCA3542) antibodies to underline its specificity towards oligomers. Results: In synthetic preparations of " monomeric" A b 1-42, a range of all sizes of oligomers are formed after 15 min incubation at 37 C. In synthetic preparations of ADDLs, different types of oligomers, displaying different immunoreactivity profiles are formed depending on the final A b concentration of the samples tested. In brain homogenates of transgenic mice, we found in the extracellular soluble enriched fraction fewer types of oligomers then what was found in synthetic preparations. Among them a species corresponding to dodecameric A b has been identified.Conclusions:A b oligomers are highly unstable and are formed differently depending of the A b concentration. This degree of aggregation drives their immunoreactivity and probably their toxic properties. Interestingly oligomers formed in-vivo are very different of those formed in vitro using synthetic A b peptides suggesting the existence of partners or chaperones that stabilize and/or solubilize certain oligomeric forms in the extracellular space.