{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:07:06Z","timestamp":1785409626129,"version":"3.56.0"},"posted":{"date-parts":[[2025,10,3]]},"group-title":"Neuroscience","reference-count":18,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["AG081037"],"award-info":[{"award-number":["AG081037"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NS132483"],"award-info":[{"award-number":["NS132483"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["HL171505"],"award-info":[{"award-number":["HL171505"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["EY034116"],"award-info":[{"award-number":["EY034116"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NS047101"],"award-info":[{"award-number":["NS047101"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["AG062429"],"award-info":[{"award-number":["AG062429"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Astrocytes and microglia play crucial roles in mediating neuroinflammation during Alzheimer\u2019s disease (AD) progression. ApoA-I binding protein (APOA1BP, also known as AIBP\/NAXE) attenuates neuroinflammation by blocking amyloid \u03b2-induced TLR4 inflammaraft formation and oxidative stress.\n                  <jats:italic>Apoa1bp<\/jats:italic>\n                  knockout in APP\/PS1 mice exacerbates microgliosis, increases amyloid plaque burden, neuronal cell loss, and reduces survival at 6 months. Although\n                  <jats:italic>APOA1BP<\/jats:italic>\n                  mRNA is ubiquitously expressed in humans, its cell-type-specific distribution in the brain remains unclear. To examine AIBP protein expression in the human brain, we performed immunohistochemistry on hippocampal sections from postmortem brain specimens from subjects aged 75-96 of both sexes. Using GFAP and IBA1 to label astrocytes and microglia, respectively, we found that AIBP protein was highly expressed in astrocytes, but not in microglia. Stratification of subjects by Braak stage (I-II, III-IV, V-VI) revealed a progressive decline in astrocytic AIBP expression with advancing AD pathology. Meta-analysis of RNA-seq profiling indicated enriched\n                  <jats:italic>Apoa1bp<\/jats:italic>\n                  expression in adult mouse astrocytes. Systemic\n                  <jats:italic>Apoa1bp<\/jats:italic>\n                  knockout in the APP\/PS1 mouse exacerbated astrogliosis. These findings demonstrate that AIBP is predominantly expressed in astrocytes and its expression declines with AD progression, suggesting a potential role for AIBP in astrocyte-mediated neuroprotection and AD pathogenesis.\n                <\/jats:p>","DOI":"10.1101\/2025.10.03.680289","type":"posted-content","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T02:20:20Z","timestamp":1759544420000},"source":"Crossref","is-referenced-by-count":0,"title":["Progressive Loss of Astrocytic AIBP Expression during Alzheimer\u2019s Disease Pathology"],"prefix":"10.64898","author":[{"given":"Shihui","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1152-1509","authenticated-orcid":false,"given":"Soo-Ho","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4477-0018","authenticated-orcid":false,"given":"Yi Sak","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaus","family":"Nazarenkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-7690","authenticated-orcid":false,"given":"Yury I.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100717252422000_2025.10.03.680289v1.1","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Giraldo, M. ; Gonz\u00e1lez-Reyes, R. E. ; Ram\u00edrez-Guerrero, S. ; Bonilla-Trilleras, C. E. ; Guardo-Maya, S. ; Nava-Mesa, M. O. , Astrocytes as a Therapeutic Target in Alzheimer\u2019s Disease-Comprehensive Review and Recent Developments. Int J Mol Sci 2022, 23, (21).","DOI":"10.3390\/ijms232113630"},{"issue":"1","key":"2025100717252422000_2025.10.03.680289v1.2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s12276-023-01148-0","article-title":"Pathological phenotypes of astrocytes in Alzheimer\u2019s disease","volume":"56","year":"2024","journal-title":"Experimental & Molecular Medicine"},{"key":"2025100717252422000_2025.10.03.680289v1.3","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6761"},{"key":"2025100717252422000_2025.10.03.680289v1.4","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.TR119000468"},{"issue":"1","key":"2025100717252422000_2025.10.03.680289v1.5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12974-024-03214-4","article-title":"AIBP controls TLR4 inflammarafts and mitochondrial dysfunction in a mouse model of Alzheimer\u2019s disease","volume":"21","year":"2024","journal-title":"J Neuroinflammation"},{"key":"2025100717252422000_2025.10.03.680289v1.6","doi-asserted-by":"crossref","unstructured":"Ding, S. ; Choi, S. H. ; Miller, Y. I. , Amyloid \u03b2-Induced Inflammarafts in Alzheimer\u2019s Disease. Int J Mol Sci 2025, 26, (10).","DOI":"10.3390\/ijms26104592"},{"key":"2025100717252422000_2025.10.03.680289v1.7","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M083618"},{"issue":"1","key":"2025100717252422000_2025.10.03.680289v1.8","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1750-1326-6-85","article-title":"Adult hippocampal neurogenesis and its role in Alzheimer\u2019s disease","volume":"6","year":"2011","journal-title":"Molecular Neurodegeneration"},{"key":"2025100717252422000_2025.10.03.680289v1.9","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315485"},{"key":"2025100717252422000_2025.10.03.680289v1.10","doi-asserted-by":"crossref","unstructured":"Navia-Pelaez, J. M. ; Choi, S. H. ; Dos Santos Aggum Capettini, L. ; Xia, Y. ; Gonen, A. ; Agatisa-Boyle, C. ; Delay, L. ; Goncalves Dos Santos, G. ; Catroli, G. F. ; Kim, J. ; Lu, J. W. ; Saylor, B. ; Winkels, H. ; Durant, C. P. ; Ghosheh, Y. ; Beaton, G. ; Ley, K. ; Kufareva, I. ; Corr, M. ; Yaksh, T. L. ; Miller, Y. I. , Normalization of cholesterol metabolism in spinal microglia alleviates neuropathic pain. 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H. ; Wallace, A. M. ; Schneider, D. A. ; Burg, E. ; Kim, J. ; Alekseeva, E. ; Ubags, N. D. ; Cool, C. D. ; Fang, L. ; Suratt, B. T. ; Miller, Y. I. , AIBP augments cholesterol efflux from alveolar macrophages to surfactant and reduces acute lung inflammation. JCI Insight 2018, 3, (16).","DOI":"10.1172\/jci.insight.120519"},{"issue":"8","key":"2025100717252422000_2025.10.03.680289v1.17","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1016\/j.ymthe.2025.05.009","article-title":"Restoring AIBP expression in the retina provides neuroprotection in glaucoma","volume":"33","year":"2025","journal-title":"Mol Ther"},{"key":"2025100717252422000_2025.10.03.680289v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.10.03.680289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:44:05Z","timestamp":1768470245000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.10.03.680289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":18,"URL":"https:\/\/doi.org\/10.1101\/2025.10.03.680289","relation":{},"subject":[],"published":{"date-parts":[[2025,10,3]]},"subtype":"preprint"}}