Picomolar Amyloid-β Positively Modulates Synaptic Plasticity and Memory in Hippocampus

TLDR

Amyloid‑β peptides are overproduced in Alzheimer’s disease, impairing synaptic function, yet are also normally released in small amounts during synaptic activity. The effect of picomolar Aβ42 on hippocampal plasticity and memory is mediated by α7‑containing nicotinic acetylcholine receptors. Low picomolar concentrations of Aβ42 enhance hippocampal long‑term potentiation and both reference and contextual fear memory, whereas high nanomolar levels reduce potentiation, supporting a dual modulatory role of Aβ.

Abstract

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 Aβ 42 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 Aβ 42 also produce a pronounced enhancement of both reference and contextual fear memory. The mechanism of action of picomolar Aβ 42 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.