Cognitive effects of cell-derived and synthetically derived Aβ oligomers

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.