Archive ScienceWatch



Dominic M. Walsh & Dennis J. Selkoe talk with and answer a few questions about this month's Emerging Research Front in the field of Neuroscience & Behavior.
Walsh Article: Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo
Authors: Walsh, DM;Klyubin, I;Fadeeva, JV;Cullen, WK;Anwyl, R;Wolfe, MS;Rowan, MJ;Selkoe, DJ
Journal: NATURE, 416 (6880): 535-539 APR 4 2002
Addresses: Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
Univ Dublin Trinity Coll, Dept Pharmacol & Therapeut, Dublin 2, Ireland.
(addresses may have been truncated.)

Why do you think your paper is highly cited?

There are two key reasons: firstly, Alzheimer's Disease (AD) involves compromise of synaptic function and memory and, in this paper, we demonstrate that certain forms of the AD-associated amyloid ß-protein (Aß) can compromise long-term potentiation (LTP), a measure of synaptic efficacy and a correlate of memory and learning.

Secondly, Aß can self-associate and aggregate to form a number of different structural assemblies and there has been much contention as to which of these species are pathogenic. In Walsh et al. we provide clear evidence that a soluble non-fibrillar form of cell-derived Aß can perturb LTP in the rat.

Does it describe a new discovery, methodology, or synthesis of knowledge?

The methods used were not novel, but their application was new, i.e., we tested the effect of two discrete types of Aß (monomer and SDS-stable low-n oligomers) on LTP.

Would you summarize the significance of your paper in layman's terms?

This work suggests that the amyloid ß-protein is responsible for the memory loss that characterizes AD.

How did you become involved in this research and were any particular problems encountered along the way?

Professor Selkoe undertook a research fellowship after completing his medical degree and training as a neurologist. Professor Walsh studied biochemistry as an undergraduate and then completed a Ph.D. in biochemistry. Both Professors Selkoe and Walsh have spent their working life researching the molecular basis of AD.

Where do you see your research leading in the future?

Our research efforts are aimed to elucidate the molecular events which trigger AD in the hope that we can identify useful therapeutic targets.

Do you foresee any social or political implications for your research?

AD is a growing scourge which places a huge burden on society and health care providers. Without an effective treatment this burden will steadily increase as the world's population continues to age. Thus it is essential that useful new therapeutics be developed as rapidly as possible. By highlighting the role of soluble Aß in AD we hope we may have speeded this development.

Dominic M. Walsh, Ph.D.
Associate Professor of Neurodegeneration
Laboratory for Neurodegenerative Research
School of Biomolecular and Biomedical Science
Conway Institute of Biomolecular and Biomedical Research
University College Dublin
Belfield, Dublin, Republic of Ireland

Dennis J. Selkoe M.D.
Center for Neurologic Diseases
Brigham and Women's Hospital
Harvard Institutes of Medicine
Boston, MA, USA

Related Information:

Keywords: naturally secreted oligomers, amyloid beta protein, amyloid ß-protein, hippocampal long-term potentiation, Alzheimer's Disease (AD), AD-associated amyloid ß-protein (Aß), can compromise long-term potentiation (LTP), synaptic efficacy, cell-derived Aß.


2008 : June 2008 : Dominic Walsh & Dennis J. Selkoe