{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:02:10Z","timestamp":1784293330228,"version":"3.55.0"},"reference-count":62,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T00:00:00Z","timestamp":1710892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U54 AG054349"],"award-info":[{"award-number":["U54 AG054349"]}],"id":[{"id":"10.13039\/100000049","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":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Variants in <jats:italic>ABCA7<\/jats:italic>, a member of the ABC transporter superfamily, have been associated with increased risk for developing late onset Alzheimer's disease (LOAD).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>CRISPR\u2010Cas9 was used to generate an <jats:italic>Abca7<jats:sup>V1613M<\/jats:sup><\/jats:italic> variant in mice, modeling the homologous human <jats:italic>ABCA7<jats:sup>V1599M<\/jats:sup><\/jats:italic> variant, and extensive characterization was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p><jats:italic>Abca7<jats:sup>V1613M<\/jats:sup><\/jats:italic> microglia show differential gene expression profiles upon lipopolysaccharide challenge and increased phagocytic capacity. Homozygous <jats:italic>Abca7<jats:sup>V1613M<\/jats:sup><\/jats:italic> mice display elevated circulating cholesterol and altered brain lipid composition. When crossed with 5xFAD mice, homozygous <jats:italic>Abca7<jats:sup>V1613M<\/jats:sup><\/jats:italic> mice display fewer Thioflavin S\u2010positive plaques, decreased amyloid beta (A\u03b2) peptides, and altered amyloid precursor protein processing and trafficking. They also exhibit reduced A\u03b2\u2010associated inflammation, gliosis, and neuronal damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Overall, homozygosity for the <jats:italic>Abca7<jats:sup>V1613M<\/jats:sup><\/jats:italic> variant influences phagocytosis, response to inflammation, lipid metabolism, A\u03b2 pathology, and neuronal damage in mice. This variant may confer a gain of function and offer a protective effect against Alzheimer's disease\u2010related pathology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:italic>ABCA7<\/jats:italic> recognized as a top 10 risk gene for developing Alzheimer's disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Loss of function mutations result in increased risk for LOAD.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>V1613M variant reduces amyloid beta plaque burden in 5xFAD mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>V1613M variant modulates APP processing and trafficking in 5xFAD mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>V1613M variant reduces amyloid beta\u2010associated damage in 5xFAD mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13783","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T09:59:28Z","timestamp":1710928768000},"page":"4914-4934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The <i>Abca7<sup>V1613M<\/sup><\/i> variant reduces A\u03b2 generation, plaque load, and neuronal damage"],"prefix":"10.1002","volume":"20","author":[{"given":"Claire A.","family":"Butler","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"},{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Mendoza Arvilla","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giedre","family":"Milinkeviciute","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Da Cunha","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimako","family":"Kawauchi","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"},{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narges","family":"Rezaie","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology University of California  Irvine California USA"},{"name":"Center for Complex Biological Systems University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi Y.","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology University of California  Irvine California USA"},{"name":"Center for Complex Biological Systems University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Javonillo","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Thach","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuling","family":"Wang","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherilyn","family":"Collins","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Walker","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Xuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Neumann","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Gomez\u2010Arboledas","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caden M.","family":"Henningfield","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay A.","family":"Hohsfield","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Mapstone","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"},{"name":"Department of Neurology University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Tenner","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"},{"name":"Department of Molecular Biology &amp; Biochemistry University of California  Irvine California USA"},{"name":"Department of Pathology and Laboratory Medicine University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"LaFerla","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"},{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Mortazavi","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology University of California  Irvine California USA"},{"name":"Center for Complex Biological Systems University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant R.","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Transgenic Mouse Facility, ULAR, Office of Research University of California  Irvine California USA"},{"name":"Department of Developmental and Cell Biology University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim N.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior University of California  Irvine California USA"},{"name":"Institute for Memory Impairments and Neurological Disorders University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00269-y"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2802"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2973"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24466"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.803"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.05099.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2022.159157"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12172143"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307831200"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.145316"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309888200"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3757-15.2016"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40273"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcac120"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200601030"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4165-12.2013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908529116"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160456"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.655076"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01346-3"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2016.04.004"},{"key":"e_1_2_9_23_1","article-title":"PyWGCNA: a Python package for weighted gene co\u2010expression network analysis","author":"Rezaie N","year":"2022","journal-title":"bioRxiv"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00313"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b03404"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-021-01054-y"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.785276"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00598-4"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039967"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.10.002"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwi151"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.004"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-0818-1"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.018"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.801"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00133-7"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2017.04.014"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000079"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3246"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000126"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2017.07.001"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1714-x"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02459-8"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12220"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01208-7"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000141"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly098"},{"key":"e_1_2_9_49_1","article-title":"Association of common and rare variants with Alzheimer's Disease in over 13,000 diverse individuals with whole\u2010genome sequencing from the Alzheimer's disease sequencing project","author":"Lee WP","year":"2023","journal-title":"medRxiv"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860-14.2014"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-01994-1"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1195-2"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00894-z"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa182"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00764-7"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412602200"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2008.05433.x"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170883"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2013.09.040"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.4198"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034406"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14323"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00790"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.13783","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:54:48Z","timestamp":1759931688000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.13783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,20]]},"references-count":62,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/alz.13783"],"URL":"https:\/\/doi.org\/10.1002\/alz.13783","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,20]]},"assertion":[{"value":"2023-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}