{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T07:34:54Z","timestamp":1790926494168,"version":"4.1.0"},"reference-count":76,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Transferrin receptor (TfR)-targeting of biologics has emerged as a promising strategy to improve drug delivery across the blood-brain barrier (BBB). However, most preclinical studies evaluating TfR-enabled drugs have been conducted in young adult animals. It remains unclear whether age and aging-related diseases impact TfR protein levels and\/or BBB transport capacity. Here, we utilized a previously described TfR-targeting antibody transport vehicle (ATV\n                    <jats:sup>TfR<\/jats:sup>\n                    ) to investigate how healthy aging and disease progression in the 5xFAD mouse model of Alzheimer\u2019s disease (AD) impact TfR protein and TfR-mediated brain delivery. ATV\n                    <jats:sup>TfR<\/jats:sup>\n                    transport capacity remained stable across 3- to 24-month-old healthy mice and 5xFAD progression did not impair ATV\n                    <jats:sup>TfR<\/jats:sup>\n                    brain transport up to 10.5 months, despite significant amyloid burden. Interestingly, neonates exhibited significantly elevated levels of vascular TfR protein and ATV\n                    <jats:sup>TfR<\/jats:sup>\n                    brain exposure compared to adult mice. Furthermore, vascular TfR in AD patient brains was similar to age-matched controls, suggesting conserved TfR transport is also likely in human AD. Overall, our data demonstrates broad functional utility for TfR-based brain delivery in both healthy aging and in an AD mouse model. Additionally, elevated TfR-mediated brain delivery during early mouse development highlights the potential of added efficacy in utilizing such platforms in disease treatment of infants and children.\n                  <\/jats:p>","DOI":"10.1177\/0271678x251361997","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T09:49:42Z","timestamp":1755337782000},"page":"20-35","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":11,"title":["Transferrin receptor-mediated transport at the blood-brain barrier is elevated during early development and maintained across aging and in an Alzheimer\u2019s mouse model"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-7560","authenticated-orcid":false,"given":"Vanessa O","family":"Torres","sequence":"first","affiliation":[{"name":"Denali Therapeutics, South San Francisco, CA, 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