Amyloid Precursor Protein Protects Neuronal Network Function after Hypoxia via Control of Voltage-Gated Calcium Channels.

Amyloid precursor protein (APP) is involved in the pathophysiology of Alzheimer's disease, but its normal function in the brain remains elusive. Here, we describe a neuroprotective role of the protein in acute hypoxia. Functional recovery of mouse hippocampal networks after transient reduction of oxygen supply was strongly impaired in animals lacking APP. Most protective effects are mediated by the soluble extracellular fragment APPsα and involve L-type calcium channels. Thus, APP contributes to calcium homeostasis in situations of metabolic stress. This finding may shed light on the physiological function of APP and may be important for understanding mechanisms of neurodegenerative diseases.