Cognitive effects of cell-derived and synthetically derived Aβ oligomers

NEUROBIOLOGY OF AGING

卷:32

Article

Reed, Miranda N.^2,3  Jungbauer, Lisa⁴  Welzel, Alfred T.⁵  Yu, Chunjiang⁴  Sherman, Mathew A.^2,3  Lesne, Sylvain^2,3  LaDu, Mary Jo⁴  Walsh, Dominic M.⁵  Ashe, Karen H.^2,3  Cleary, James P.^1,3,6 

[1] VA Med Ctr, GRECC 11G, Geriatr Res Educ & Clin Ctr, Minneapolis, MN 55417 USA

[2] Univ Minnesota, N Bud Grossman Ctr, Minneapolis, MN 55455 USA

[3] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA

[4] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60607 USA

[5] Univ Coll Dublin, Conway Inst, Lab Neurodegenerat Res, Dublin 4, Ireland

[6] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA

关键词: Alzheimer's disease;    Amyloid-beta peptide;    A beta;    Oligomers;    Cognition;   

DOI  :  10.1016/j.neurobiolaging.2009.11.007

来源: Elsevier

【 摘 要 】

Soluble forms of amyloid-beta peptide (A beta) are a molecular focus in Alzheimer's disease research. Soluble A beta dimers (approximate to 8 kDa), trimers (approximate to 12kDa), tetramers (approximate to 16 kDa) and A beta*56 (approximate to 56kDa) have shown biological activity. These A beta molecules have been derived from diverse sources, including chemical synthesis, transfected cells, and mouse and human brain, leading to uncertainty about toxicity and potency. Herein, synthetic A beta peptide-derived oligomers, cell- and brain-derived low-n oligomers, and A beta*56, were injected intracerebroventricularly (icy) into rats assayed under the Alternating Lever Cyclic Ratio (ALCR) cognitive assay. Cognitive deficits were detected at 1.3 mu M of synthetic oligomers and at low nanomolar concentrations of cell-secreted A beta oligomers. Trimers, from transgenic mouse brain (Tg2576), did not cause cognitive impairment at any dose tested, whereas A beta*56 induced concentration-dependent cognitive impairment at 0.9 and 1.3 mu M. Thus, while multiple forms of A beta have cognition impairing activity, there are significant differences in effective concentration and potency. Published by Elsevier Inc.

【 授权许可】

Free