Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo

By D. Walsh, I. Klyubin, J. Fadeeva, W. K. Cullen, R. Anwyl, M. Wolfe, M. Rowan, D. Selkoe. Nature, 2002

4,448 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Pharmacology, Physiology

View Paper: https://www.semanticscholar.org/paper/4ebf1c758a2ad7e38868e772525229d3e8136c5c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. D. Selkoe
2. L. Mucke
3. D. Holtzman
4. J. Palop
5. R. Malenka
6. G. Shankar
7. C. Lüscher
8. G. Bu

In Pharmacology

1. D. Selkoe
2. L. Mucke
3. D. Holtzman
4. J. Palop
5. David B. Teplow
6. George Bartzokis
7. J. Herz
8. G. Bu

In Physiology

1. D. Selkoe
2. L. Mucke
3. D. Holtzman
4. J. Palop
5. Michael T. Heneka
6. G. Bu
7. Christopher M. Dobson
8. David B. Teplow

Citations in the corpus

• Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans (2010, background): “Why might this be? Many recent studies show that low-MW oligomers formed by diseasemisfolded proteins are at least as, if not more, toxic as high-MW, visible, aggregates [43,84,85,86].”
• Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway (2007, background): “Consistent with our model, A oligomers produced by 7PA2 cells have been previously shown to inhibit hippocampal LTP induction in vivo and in vitro and to interfere with the performance of trained rats on a memory recall task (Walsh et al., 2002, 2005; Cleary et al., 2005; Klyubin et al., 2005).”
• NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). (2012, background): “…well before this stage, and there is growing evidence that one of the toxic protein species believed to be etiologically related to AD, soluble Ab oligomers, causes early memory problems by disrupting LTP and LTD mechanisms (Walsh et al. 2002; Tanzi 2005; Shankar et al. 2008; Cisse et al. 2011).”
• Protection of synapses against Alzheimer's-linked toxins: Insulin signaling prevents the pathogenic binding of Aβ oligomers (2009, background): “The attack on synapses inhibits long-term potentiation (LTP) (11, 13, 14), a classic paradigm for memory-related synaptic mechanisms.”
• Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism (2013, neutral): “(2005) 3D structure of Alzheimer’s amyloid-beta(1-42) fibrils.”
• Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers (2006, background): “…at low nanomolar to high picomolar concentrations, similar to those in human brain and cerebrospinal fluid (Motter et al. 1995; Mehta et al. 2000; Walsh et al. 2002), whereas synthetic Aβ typically needs to be applied to neurons at 2–4 orders of magnitude higher concentrations to achieve similar…”