{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:51:11Z","timestamp":1791809471962,"version":"4.3.4"},"reference-count":57,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"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":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Soluble amyloid-\u03b2 oligomers (A\u03b2o) are considered the most neurotoxic species of A\u03b2 and key drivers of Alzheimer's disease (AD) pathogenesis. Selective targeting of A\u03b2o offers a promising therapeutic strategy. We previously identified an amyloid-binding peptide (ABP) that binds A\u03b2o and engages A\u03b2 deposits in AD mouse and human brain tissue. To facilitate brain penetration, ABP was fused to the blood-brain barrier (BBB) transporter FC5 and an Fc fragment, generating BBB-permeable constructs (mouse FC5-mFc2a-ABP and humanized FC5-hFc-ABP, referred to as BBB-ABP). Previous in vivo studies demonstrated the ability of BBB-enabled ABP to engage and clear A\u03b2 from the central nervous system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to evaluate the in vitro functionality of BBB-ABP and its ability to prevent A\u03b2o-induced neurotoxicity and synaptic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Binding specificity was assessed using ELISA and western blot overlay assays. Functional assays were performed in SH-SY5Y cells and primary neurons to evaluate A\u03b2o sequestration, protection against A\u03b2o-induced toxicity, and effects on synaptic activity measured via multi-electrode arrays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BBB-ABP retained selective binding to A\u03b2o and effectively prevented its interaction with neuronal proteins and its binding to dendritic spines in live primary neurons. BBB-ABP significantly reduced A\u03b2o-induced toxicity in SH-SY5Y cells and primary neurons, including under conditions of NMDA-induced stress. A\u03b2 exposure did not significantly alter spontaneous synaptic activity, precluding assessment of electrophysiological rescue by BBB-ABP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that BBB-ABP maintains A\u03b2o-selective binding and is capable of preventing the interaction of A\u03b2o with neurons, thereby mitigating A\u03b2o-induced toxicity in vitro, supporting its further development as a therapeutic candidate for AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261453068","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:53:43Z","timestamp":1782827623000},"page":"1774-1790","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The blood-brain barrier-penetrating fusion protein BBB-ABP selectively binds amyloid-\u03b2 oligomers and prevents in vitro neurotoxicity"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9216-2514","authenticated-orcid":false,"given":"Kerry","family":"Rennie","sequence":"first","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-0487","authenticated-orcid":false,"given":"Joseph S.","family":"Tauskela","sequence":"additional","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"M\u00e9nard","sequence":"additional","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Aylsworth","sequence":"additional","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Comas","sequence":"additional","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Whitfield","sequence":"additional","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0844-3968","authenticated-orcid":false,"given":"Balu","family":"Chakravarthy","sequence":"additional","affiliation":[{"name":"National Research Council"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.848215"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15007"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126355"},{"key":"e_1_3_3_5_2","article-title":"Relationship between efficacy and preferential targeting of soluble A\u03b2 aggregates","volume":"11","author":"Kaplan JM","year":"2025","unstructured":"Kaplan JM, Gibbs E, Coutts JA, et al. 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