Picomolar amyloid-β positively modulates synaptic plasticity and memory in hippocampus

By D. Puzzo, L. Privitera, E. Leznik, Mauro Fa’, Agnieszka Staniszewski, A. Palmeri, O. Arancio. Journal of Neuroscience, 2008

728 citations recorded by the source corpus.

Amyloid-β (Aβ) peptides are produced in high amounts during Alzheimer's disease, causing synaptic and memory dysfunction. However, they are also released in lower amounts in normal brains throughout life during synaptic activity. Here we show that low picomolar concentrations of a preparation containing both Aβ42 monomers and oligomers cause a marked increase of hippocampal long-term potentiation, whereas high nanomolar concentrations lead to the well established reduction of potentiation. Picomolar levels of Aβ42 also produce a pronounced enhancement of both reference and contextual fear memory. The mechanism of action of picomolar Aβ42 on both synaptic plasticity and memory involves α7-containing nicotinic acetylcholine receptors. These findings strongly support a model for Aβ effects in which low concentrations play a novel positive, modulatory role on neurotransmission and memory, whereas high concentrations play the well known detrimental effect culminating in dementia.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/3bcacd92c468da77bad0c77c1375e68456975318

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. J. Herz
2. G. Bu
3. D. Holtzman

In Molecular Biology

1. C. Duyckaerts
2. Yan Zhao
3. G. Bu
4. Baolu Zhao
5. D. Holtzman

In Physiology

1. J. Herz
2. D. Holtzman
3. G. Bu
4. C. Duyckaerts
5. Marie-Claude Potier
6. Yan Zhao
7. Benoit Delatour
8. Baolu Zhao

Citations in the corpus

• Apolipoprotein E and apolipoprotein E receptors: normal biology and roles in Alzheimer disease. (2012, background): “…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 Strittmatter 2009; Gimbel et al. 2010; Palop and Mucke 2010; Renner et al. 2010; Ronicke et al.…”
• APP processing in Alzheimer's disease (2011, background): “novel positive, modulatory role on neurotransmission and memory [158,159].”
• Amyloid β-based therapy for Alzheimer’s disease: challenges, successes and future (2023, background): “To address this concern, other studies injected picomolar concentrations of Aβ peptides into the mice, which also significantly enhanced synaptic plasticity and memory formation.(394) These findings suggest that physiological levels of Aβ monomers are crucial to maintain a normal synaptic function w”
• Classification and basic pathology of Alzheimer disease (2009, background): “It has recently been found to act positively on synapses at picomolar concentration [266].”
• Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline (2016, neutral): “Additional studies demonstrate that Abeta oligomers are ligands for nAChRs, and in the case of α7*nAChRs, low concentrations of Abeta (in the pM range) serve as agonist, whereas in the nM range Abeta is an antagonist (Puzzo et al., 2008).”
• Oxidative Stress and the Pathogenesis of Alzheimer's Disease (2013, background): “…of Abeta and tau proteins in the induction of redox imbalance and the generation of free radicals throughmechanisms such as mitochondria dysfunction and/or transitionmetal homeostasis imbalance and discusses the mechanisms by which oxidative stress promotes Abetaand tau-mediated neurotoxicity.”