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Our recent development of genetically encoded F\u00f6rster resonance energy transfer (FRET)-based biosensors has enabled the spatiotemporal recording of \u03b3-secretase activity on a cell-by-cell basis in live neurons\n                    <jats:italic>in culture<\/jats:italic>\n                    . Nevertheless, how \u03b3-secretase activity is regulated\n                    <jats:italic>in vivo<\/jats:italic>\n                    remains unclear. Here, we employ the near-infrared (NIR) C99 720\u2013670 biosensor and NIR confocal microscopy to quantitatively record \u03b3-secretase activity in individual neurons in living mouse brains. Intriguingly, we uncovered that \u03b3-secretase activity may influence the activity of \u03b3-secretase in neighboring neurons, suggesting a potential \u2018cell non-autonomous\u2019 regulation of \u03b3-secretase in mouse brains. Given that \u03b3-secretase plays critical roles in important biological events and various diseases, our new assay\n                    <jats:italic>in vivo<\/jats:italic>\n                    would become a new platform that enables dissecting the essential roles of \u03b3-secretase in normal health and diseases.\n                  <\/jats:p>","DOI":"10.7554\/elife.96848","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T09:25:14Z","timestamp":1714123514000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.96848","source":"Crossref","is-referenced-by-count":3,"title":["Recording \u03b3-secretase activity in living mouse brains"],"prefix":"10.7554","volume":"13","author":[{"given":"Steven S","family":"Hou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical 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