{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:34:06Z","timestamp":1791588846440,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","award":["UKDRI\u2010Edin0010"],"award-info":[{"award-number":["UKDRI\u2010Edin0010"]}],"id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1165504"],"award-info":[{"award-number":["APP1165504"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Dendritic spine loss in Alzheimer's disease (AD) strongly correlates with cognitive decline, whereas spine preservation is associated with cognitive resilience. Yet, whether and how neurons compensate for spine loss in AD remains largely unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We developed a chromophore\u2010assisted light inactivation (CALI) strategy to selectively eliminate dendritic spines to model this key feature of AD. Two\u2010photon microscopy was used to monitor the structural plasticity of spines over time after spine elimination. Validation experiments were conducted in amyloid beta (A\u03b2)\u2013driven models of synapse loss, including APP\/PS1 mice and intracortical delivery of oligomeric A\u03b2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We discovered that dendritic spine elimination\u2014induced either artificially or in A\u03b2 models\u2014triggers a two\u2010stage compensatory response: rapid enlargement of remaining spines followed by delayed spine regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings provide direct evidence that neurons retain an intrinsic capacity to reverse early synaptic loss in AD, potentially contributing to cognitive resilience.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We developed a targeted optogenetic tool to selectively eliminate individual dendritic spines in live neurons, both in vitro and in vivo.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We discovered a two\u2010stage compensatory response to spine loss: rapid enlargement of surviving spines followed by delayed regeneration.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We showed that the compensatory enlargement of dendritic spines\u00a0depends on N\u2010methyl\u2010D\u2010aspartate receptor activation and protein synthesis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We validated across multiple Alzheimer's disease models, demonstrating that similar compensatory plasticity occurs after amyloid beta oligomer\u2013induced synapse loss.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We postulate that synaptic resilience is an active neuronal program rather than a passive byproduct of pathology.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70829","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T03:25:02Z","timestamp":1761276302000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Direct evidence for dendritic spine compensation and regeneration in Alzheimer's disease models"],"prefix":"10.1002","volume":"21","author":[{"given":"Nishita","family":"Bhembre","sequence":"first","affiliation":[{"name":"Clem Jones Centre for Ageing Dementia Research Queensland Brain Institute The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Boskovic","sequence":"additional","affiliation":[{"name":"Clem Jones Centre for Ageing Dementia Research Queensland Brain Institute The University of Queensland  Brisbane Queensland Australia"},{"name":"School of Psychology and Public Health La Trobe University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Louise","family":"Willshaw","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute Institute for Neuroscience and Cardiovascular Research University of Edinburgh  Edinburgh 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