Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers

By Matthew Townsend, G. Shankar, Tapan H. Mehta, D. Walsh, D. Selkoe. Journal of Physiology, 2006

645 citations recorded by the source corpus.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Physiology

View Paper: https://www.semanticscholar.org/paper/6af91c69e3d82c902dc57caf13c8eb4a7737506d

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. D. Holtzman
3. G. Shankar
4. G. Bu
5. P. Reddy
6. Nina E. Shepardson
7. Shaomin Li
8. C. Parsons

In Cognitive Neuroscience

1. D. Selkoe
2. G. Shankar
3. Bernardo L. Sabatini
4. D. Holtzman

In Physiology

1. D. Selkoe
2. D. Holtzman
3. G. Bu
4. P. Reddy
5. G. Shankar
6. J. Herz
7. K. Viola
8. D. Walsh

Citations in the corpus

• Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “Aβ oligomers change the morphology and density of synapses, leading to the impairment of synaptic plasticity.(76,77) As a glutamate receptor, functional NMDARs regulate the formation of synapes and synaptic plasticity.”
• The Diabetes Drug Liraglutide Prevents Degenerative Processes in a Mouse Model of Alzheimer's Disease (2011, background): “Aggregated amyloid species are considered to be toxic and more detrimental to neuronal development than plaques (Townsend et al., 2006).”
• Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. (2012, background): “…have been proposed to explain this effect (Lambert et al. 1998; Walsh et al. 2002; Lacor et al. 2004; Snyder et al. 2005; Lesne et al. 2006; Townsend et al. 2006; Haass and Selkoe 2007; Shankar et al. 2007; Berman et al. 2008; Puzzo et al. 2008; Shankar et al. 2008; Nygaard and…”
• Aβ Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease (2007, background): “It has been reported that trimers that form in cell-conditioned culture medium also show neurological effects (Townsend et al., 2006).”
• Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors (2011, methodology): “Experimentally, soluble A oligomers (but not monomers) have been found to block hippocampal long-term potentiation (LTP), a synaptic correlate of memory and learning (Lambert et al., 1998; Walsh et al., 2002; Wang et al., 2002; Klyubin et al., 2005; Townsend et al., 2006; Shankar et al., 2007, 2008)”
• Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system--too little activation is bad, too much is even worse. (2007, positive): “More recent publications confirm this finding (Walsh et al., 2005; Townsend et al., 2006; Puzzo and Arancio, 2006).”
• Soluble oligomers of amyloid β-protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake (2009, positive): “Experimentally, soluble Aβ oligomers have been specifically shown to block hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory (e.g., Lambert et al, 1998; Walsh et al., 2002; Wang et al., 2002; Townsend et al., 2006; Shankar et al, 2008).”
• Natural Oligomers of the Alzheimer Amyloid-β Protein Induce Reversible Synapse Loss by Modulating an NMDA-Type Glutamate Receptor-Dependent Signaling Pathway (2007, methodology): “NMDAR activation can induce LTP or LTD, depending on the concentration and kinetics of downstream postsynaptic Ca elevations.”
• The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade (2018, background): “Long-term potentiation (LTP) and long-term depression, the electrophysiological underpinnings of memory formation, are disrupted by A Os both ex vivo and in vivo [26, 36, 37, 40, 41].”
• Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior. (2008, methodology): “We have also developed protocols for separating the secreted oligomers by SEC under non-denaturing conditions (Klyubin et al. 2005; Townsend et al. 2006; Walsh et al. 2005).”
• Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. (2008, background): “Further, recent electrophysiology data also suggest that a trimeric form of Aβ inhibits long-term potentiation in rodents [40].”