One of my strongest memories of my undergraduate degree is the first time I looked down the microscope at the brain of an individual who had died from Alzheimer’s disease. Dense, tangled clumps of protein, amyloid plaques, littered the brain like black mould; an enemy in plain sight. Since amyloid-β (Aβ) was identified as the principal component of amyloid plaques, countless studies have shown that high levels of Aβ are toxic to neurons and can severely disrupt synaptic function. Surely, then, we just need to remove this invader from our brains, and we will have our cure for Alzheimer’s disease?

In this study, Puzzo et al. replicated work (reported by many groups including the Klein, Xie, and Selkoe labs) to show that high (nanomolar) concentrations of Aβ could disrupt long-term potentiation, a measure of synapse strength thought to underlie learning and memory — so far, as expected. However, when slices of mouse hippocampus were exposed to much lower levels of Aβ (200 pM), similar to levels found in healthy brains, the authors observed that long-term potentiation was enhanced. When infusing the hippocampus of live mice with low levels of Aβ, they found that this improved performance in several memory tasks. As other studies had shown that the levels of extracellular Aβ are regulated by neuronal activity, the authors proposed that Aβ supports learning and memory under physiological conditions. A year later it was reported that depletion of endogenous Aβ from wild-type mouse brains disrupts performance on a memory task (Garcia-Osta et al., 2009) and another group found that Aβ has important roles in regulating synaptic transmission (Abramov et al., 2009).