A vicious cycle of β amyloid–dependent neuronal hyperactivation

<jats:title>Dissecting hyperactivation in AD</jats:title> <jats:p> Progressive accumulation of amyloid β (Aβ) in the brain is a defining feature of Alzheimer's disease (AD). At late stages of AD, pathological Aβ accumulations cause neurodegeneration and cell death. However, neuronal dysfunction, consisting of an excessively increased activity in a fraction of brain neurons, already occurs in early stages of the disease. Zott <jats:italic>et al.</jats:italic> explored the cellular basis of this hyperactivity in mouse models of AD (see the Perspective by Selkoe). Aβ-mediated hyperactivation was linked to a defect in synaptic transmission exclusively in active neurons, with the most-active neurons having the highest risk of hyperactivation. Aβ-containing brain extracts from human AD patients sustained this vicious cycle, underscoring the potential relevance of this pathological mechanism in humans. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6453" page="559" related-article-type="in-this-issue" vol="365" xlink:href="10.1126/science.aay0198">559</jats:related-article> ; see also p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6453" page="540" related-article-type="in-this-issue" vol="365" xlink:href="10.1126/science.aay5188">540</jats:related-article> </jats:p>