Cognitive effects of cell-derived and synthetically derived Aβ oligomers

Miranda N. Reed, Jacki J. Hofmeister, Lisa Jungbauer, Alfred T. Welzel, Chunjiang Yu, Mathew A. Sherman, Sylvain Lesné, Mary Jo LaDu, Dominic M. Walsh, Karen H. Ashe, James P. Cleary

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Soluble forms of amyloid-β peptide (Aβ) are a molecular focus in Alzheimer's disease research. Soluble Aβ dimers (≈8. kDa), trimers (≈12. kDa), tetramers (≈16. kDa) and Aβ*56 (≈56. kDa) have shown biological activity. These Aβ 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 Aβ peptide-derived oligomers, cell- and brain-derived low-n oligomers, and Aβ*56, were injected intracerebroventricularly (icv) into rats assayed under the Alternating Lever Cyclic Ratio (ALCR) cognitive assay. Cognitive deficits were detected at 1.3 μM of synthetic Aβ oligomers and at low nanomolar concentrations of cell-secreted Aβ oligomers. Trimers, from transgenic mouse brain (Tg2576), did not cause cognitive impairment at any dose tested, whereas Aβ*56 induced concentration-dependent cognitive impairment at 0.9 and 1.3 μM. Thus, while multiple forms of Aβ have cognition impairing activity, there are significant differences in effective concentration and potency.

Original languageEnglish (US)
Pages (from-to)1784-1794
Number of pages11
JournalNeurobiology of Aging
Volume32
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Alzheimer's disease
  • Amyloid-β peptide
  • Cognition
  • Oligomers

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