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Globular amyloid β‐peptide 1−42 oligomer − a homogenous and stable neuropathological protein in Alzheimer's disease
Author(s) -
Barghorn Stefan,
Nimmrich Volker,
Striebinger Andreas,
Krantz Carsten,
Keller Patrick,
Janson Bodo,
Bahr Michael,
Schmidt Martin,
Bitner Robert S.,
Harlan John,
Barlow Eve,
Ebert Ulrich,
Hillen Heinz
Publication year - 2005
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.1471-4159.2005.03407.x
Subject(s) - oligomer , hippocampal formation , amyloid (mycology) , peptide , alzheimer's disease , p3 peptide , chemistry , epitope , long term potentiation , fibril , biophysics , biochemistry , microbiology and biotechnology , antibody , biology , amyloid precursor protein , neuroscience , pathology , immunology , medicine , disease , receptor , inorganic chemistry , organic chemistry
Amyloid β‐peptide (Aβ) 1−42 oligomers have recently been discussed as intermediate toxic species in Alzheimer's disease (AD) pathology. Here we describe a new and highly stable Aβ 1−42 oligomer species which can easily be prepared in vitro and is present in the brains of patients with AD and Aβ 1−42 ‐overproducing transgenic mice. Physicochemical characterization reveals a pure, highly water‐soluble globular 60‐kDa oligomer which we named ‘Aβ 1−42 globulomer’. Our data indicate that Aβ 1−42 globulomer is a persistent structural entity formed independently of the fibrillar aggregation pathway. It is a potent antigen in mice and rabbits eliciting generation of Aβ 1−42 globulomer‐specific antibodies that do not cross‐react with amyloid precursor protein, Aβ 1−40 and Aβ 1−42 monomers and Aβ fibrils. Aβ 1−42 globulomer binds specifically to dendritic processes of neurons but not glia in hippocampal cell cultures and completely blocks long‐term potentiation in rat hippocampal slices. Our data suggest that Aβ 1−42 globulomer represents a basic pathogenic structural principle also present to a minor extent in previously described oligomer preparations and that its formation is an early pathological event in AD. Selective neutralization of the Aβ globulomer structure epitope is expected to have a high potential for treatment of AD.