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However, the cellular impacts of amyloid precursor protein (\n                      <jats:italic>APP<\/jats:italic>\n                      ) mutations compared with age\u2010related overexpression of\n                      <jats:italic>APP<\/jats:italic>\n                      or the deposition of amyloid beta (A\u03b2) are likely different.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using high\u2010density multi\u2010electrode arrays, we compared neural activity in cultured neurons subjected to A\u03b2 exposure or\n                      <jats:italic>APP<\/jats:italic>\n                      overexpression (via lentiviral delivery or genetic models). Effects on neuronal firing, synaptogenesis, axonal branching, and network connectivity were assessed in both developing and mature cultures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APP<\/jats:italic>\n                      overexpression reduced individual neuron firing probability and impaired synaptogenesis and axonal branching during development. In contrast, A\u03b2 disrupted synaptic connections in mature cultures and impaired network\u2010level communication without blocking early structural development.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings indicate that APP mis\u2010regulation and A\u03b2 toxicity contribute differently to neuronal behavior. These differences raise questions about the assumptions that familial and sporadic AD are similar if not identical conditions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71493","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:53:42Z","timestamp":1779785622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Behavior of neural networks in culture suggest that sporadic and genetic forms of Alzheimer's disease may not be equivalent"],"prefix":"10.1002","volume":"22","author":[{"given":"Fulin","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Neurobiology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Akolkar","sequence":"additional","affiliation":[{"name":"Department of Neurobiology University of Pittsburgh School of Medicine  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