Abstract
Since its original description in 1906 by Dr Alois Alzheimer, amyloid plaques and neurofibrillary tangles have remained the hypothetical cause of Alzheimer’s disease. However, plaque burden poorly predicts cognitive status in humans, which led several groups to investigate the possibility that soluble species of amyloid-beta (Aβ) peptides could be playing an important pathological function in the aging brain. Through a multistep fractionation protocol, we identified a 56 kDa oligomer of Aβ, termed Aβ*56, the amount of which correlates with cognitive impairment. Here, we describe our biochemical approach to isolate this oligomeric Aβ species in brain tissue of transgenic mouse models of AD.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Haass, C., and Selkoe, D. J. (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8, 101–12.
Walsh, D. M., Minogue, A. M., Sala Frigerio, C., Fadeeva, J. V., Wasco, W., and Selkoe, D. J. (2007) The APP family of proteins: similarities and differences. Biochem Soc Trans 35, 416–20.
Selkoe, D. J., and Wolfe, M. S. (2007) Presenilin: running with scissors in the membrane. Cell 131, 215–21.
Lesne, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., and Ashe, K. H. (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440, 352–7.
Walsh, D. M., and Selkoe, D. J. (2007) A beta oligomers – a decade of discovery. J Neurochem 101, 1172–84.
Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., and Ashe, K. H. (2005) Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci 8, 79–84.
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., and Selkoe, D. J. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535–9.
Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., Regan, C. M., Walsh, D. M., Sabatini, B. L., and Selkoe, D. J. (2008) Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14, 837–42.
Cheng, I. H., Scearce-Levie, K., Legleiter, J., Palop, J. J., Gerstein, H., Bien-Ly, N., Puolivali, J., Lesne, S., Ashe, K. H., Muchowski, P. J., and Mucke, L. (2007) Accelerating amyloid-beta fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J Biol Chem 282, 23818–28.
Lesne, S., Kotilinek, L., and Ashe, K. H. (2008) Plaque-bearing mice with reduced levels of oligomeric amyloid-beta assemblies have intact memory function. Neuroscience 151, 745–9.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Humana Press
About this protocol
Cite this protocol
Sherman, M.A., Lesné, S.E. (2010). Detecting Aβ*56 Oligomers in Brain Tissues. In: Roberson, E. (eds) Alzheimer's Disease and Frontotemporal Dementia. Methods in Molecular Biology, vol 670. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-744-0_4
Download citation
DOI: https://doi.org/10.1007/978-1-60761-744-0_4
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-60761-743-3
Online ISBN: 978-1-60761-744-0
eBook Packages: Springer Protocols