Cognitive effects of cell-derived and synthetically derived Aβ oligomers

Neurobiol Aging. 2011 Oct;32(10):1784-94. doi: 10.1016/j.neurobiolaging.2009.11.007. Epub 2010 Jan 19.


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 1.3μM. Thus, while multiple forms of Aβ have cognition impairing activity, there are significant differences in effective concentration and potency.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / chemical synthesis*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / toxicity*
  • Amyloid beta-Protein Precursor / genetics
  • Analysis of Variance
  • Animals
  • CHO Cells / chemistry
  • Chromatography, Gel / methods
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Cricetinae
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Administration Schedule
  • Humans
  • Injections, Intraventricular / methods
  • Mice
  • Mice, Transgenic
  • Microscopy, Atomic Force / methods
  • Peptide Fragments / chemical synthesis*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / toxicity*
  • Protein Structure, Tertiary
  • Rats
  • Silver Staining
  • Transfection / methods


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • amyloid beta-protein (1-42)