{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:03:32Z","timestamp":1790334212696,"version":"4.1.0"},"reference-count":86,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82671849"],"award-info":[{"award-number":["82671849"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Preserving adult hippocampal neurogenesis alleviates cognitive deficits in Alzheimer's disease (AD), yet how biophysical alterations in such as stiffness in the neurogenic niche regulate neurogenesis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Stiffness in the hippocampal dentate gyrus subgranular cell zone (SGZ) of 5\u00d7FAD mice was measured using atomic force microscopy. Extracellular matrix (ECM) components in mice and AD patients were profiled through proteomics. Hydrogels were supplemented in the SGZ to upregulate local stiffness in wildtype mice, while glycosaminoglycanases was injected to downregulated stiffness in 5\u00d7FAD mice. Gene expression in the neurogenic lineage was analyzed through single nucleus sequencing. Conditional knockdown or overexpression of mechanosensors and\/or Yes\u2010associated protein 1 (YAP1) were achieved using viral vectors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We found SGZ stiffening occured early in 3\u2010month 5\u00d7FAD mice, associating with ECM remodeling and neurogenesis impairment. Upregulation of tissue stiffness in the SGZ of wild\u2010type mice via supplementing high\u2010density hydrogel suppressed neurogenesis, whereas downregulaion of the niche stiffness in AD mice using hyaluronidase\u20101 (HAase1) and other glycosaminoglycanases preserved neurogenesis. Single\u2010nucleus transcriptomics reveals that the HAase1 treatment reshaped transcriptome of the neural stem cells (NSCs) lineage. Specifically, we found that the integrin\u2010YAP1 mechanotransduction axis played important roles in the stiffness\u2010induced neurogenesis deficits. Conditional knockdown of both integrin \u03b21 and YAP in the NSC lineage mitigated stiffness\u2010induced deficits. Consistently, the association of ECM remodeling and neurogenesis impairments were also observed in\n                      <jats:italic>post mortem<\/jats:italic>\n                      AD patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>ECM stiffness plays as a critical regulator of hippocampal neurogenesis, providing potential targets for pro\u2010neurogenic therapeutics of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71784","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:37:01Z","timestamp":1788143821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular matrix remodeling upregulates hippocampal neurogenic niche stiffness and impairs neurogenesis in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Weiqi","family":"Sun","sequence":"first","affiliation":[{"name":"Neuroscience Research Institute and Department of Neurobiology School of Basic Medical Sciences Key Laboratory for Neuroscience Ministry of Education\/National Health Commission Peking University  Beijing P.R. 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