{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T18:49:30Z","timestamp":1771958970345,"version":"3.50.1"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG064877"],"award-info":[{"award-number":["R01AG064877"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Health","award":["P30 AG066444"],"award-info":[{"award-number":["P30 AG066444"]}]},{"name":"National Institute of Health","award":["P01 AG03991"],"award-info":[{"award-number":["P01 AG03991"]}]},{"name":"National Institute of Health","award":["P01 AG026276"],"award-info":[{"award-number":["P01 AG026276"]}]},{"name":"National Institute of Health","award":["P30 AG066468"],"award-info":[{"award-number":["P30 AG066468"]}]},{"name":"National Institute of Health","award":["U01AT000162"],"award-info":[{"award-number":["U01AT000162"]}]},{"name":"National Institute of Health","award":["UF1AG051197"],"award-info":[{"award-number":["UF1AG051197"]}]},{"name":"National Institute of Health","award":["R01AG052446"],"award-info":[{"award-number":["R01AG052446"]}]},{"name":"National Institute of Health","award":["P01AG025204"],"award-info":[{"award-number":["P01AG025204"]}]},{"name":"National Institute of Health","award":["RF1AG052525"],"award-info":[{"award-number":["RF1AG052525"]}]},{"name":"National Institute of Health","award":["R01AG052521"],"award-info":[{"award-number":["R01AG052521"]}]},{"name":"National Institute of Health","award":["AG025516"],"award-info":[{"award-number":["AG025516"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Amyloid-PET imaging tracks the accumulation of amyloid beta (A\u03b2) deposits in the brain. Amyloid plaques accumulation may begin 10 to 20\u00a0years before the individual experiences clinical symptoms associated with Alzheimer\u2019s diseases (ad). Recent large-scale genome-wide association studies reported common risk factors associated with brain amyloidosis, suggesting that this endophenotype is driven by genetic variants. However, these loci pinpoint to large genomic regions and the functional variants remain to be identified. To identify new risk factors associated with brain amyloid deposition, we performed whole-genome sequencing on a large cohort of European descent individuals with amyloid PET imaging data (n\u2009=\u20091,888). Gene-based analysis for coding variants was performed using SKAT-O for amyloid PET as a quantitative endophenotype that identified genome-wide significant association for APOE (P\u2009=\u20092.45\u00a0\u00d7\u00a010\u221210), and 26 new candidate genes with suggestive significance association (P\u2009&amp;lt;\u20095. 0\u00a0\u00d7\u200910\u221203) including SCN7A (P\u2009=\u20097.31\u00a0\u00d7\u00a010\u221205), SH3GL1 (P\u2009=\u20097.56\u00a0\u00d7\u00a010\u221204), and MFSD12 (P\u2009=\u20098.51\u00a0\u00d7\u00a010\u221204). Enrichment analysis highlighted the lipid binding pathways as associated with A\u03b2 deposition in brain driven by PITPNM3 (P\u2009=\u20094.27\u00a0\u00d7\u00a010\u221203), APOE (P\u2009=\u20092.45\u00a0\u00d7\u00a010\u221210), AP2A2 (P\u2009=\u20091.06\u00a0\u00d7\u00a010\u221203), and SH3GL1 (P\u2009=\u20097.56\u00a0\u00d7\u00a010\u221204). Overall, our data strongly support a connection between lipid metabolism and the deposition of A\u03b2 in the brain. Our study illuminates promising avenues for therapeutic interventions targeting lipid metabolism to address brain amyloidosis.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf017","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T20:20:24Z","timestamp":1738182024000},"page":"739-748","source":"Crossref","is-referenced-by-count":2,"title":["Whole-genome sequencing reveals the impact of lipid pathway and <i>APOE<\/i> genotype on brain amyloidosis"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3914-2797","authenticated-orcid":false,"given":"Maulikkumar","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyril","family":"Pottier","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Department of Neurology, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Hsien","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Pittsburgh , 130 De Soto St, Pittsburgh, PA 15261 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arda","family":"Cetin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Gorijala","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Budde","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruyu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Pittsburgh , 130 De Soto St, Pittsburgh, PA 15261 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann D","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh , 3811 O'Hara Street, Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James T","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh , 3471 Fifth Avenue, Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beth E","family":"Snitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh , 3471 Fifth Avenue, Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard","family":"Aizenstein","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, University of Pittsburgh , 130 De Soto St, Pittsburgh, PA 15261 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar L","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Pittsburgh , 3471 Fifth Avenue, Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hope Center for Neurologic Diseases, Section on Aging & Dementia, Institute of Clinical and Translational Sciences, Knight Alzheimer Disease Research Center Washington University School of Medicine , 4901 Forest Park Ave 4th floor, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M Ilyas","family":"Kamboh","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Department of Psychiatry University of Pittsburgh , 130 De Soto St, Pittsburgh, PA 15261 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Cruchaga","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurogenomics and Informatics, Department of Neurology, Hope Center for Neurologic Diseases, Knight Alzheimer Disease Research Center, Washington University School of Medicine , 4444 Forest Park Ave, St. Louis, MO 63108 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"2025040712175494600_ref1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"2025040712175494600_ref2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jalz.2012.11.007","article-title":"The global prevalence of dementia: a systematic review and metaanalysis","volume":"9","author":"Prince","year":"2013","journal-title":"Alzheimers Dement"},{"key":"2025040712175494600_ref3","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1038\/s41598-018-37769-z","article-title":"Predicting Alzheimer's disease progression using multi-modal deep learning approach","volume":"9","author":"Lee","year":"2019","journal-title":"Sci Rep"},{"key":"2025040712175494600_ref4","doi-asserted-by":"crossref","first-page":"S633","DOI":"10.3233\/JAD-179928","article-title":"Amyloid accumulation and cognitive decline in clinically normal older individuals: implications for aging and early Alzheimer's disease","volume":"64","author":"Mormino","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"2025040712175494600_ref5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/alzrt62","article-title":"Amyloid imaging and memory change for prediction of cognitive impairment","volume":"3","author":"Resnick","year":"2011","journal-title":"Alzheimers Res Ther"},{"key":"2025040712175494600_ref6","doi-asserted-by":"crossref","first-page":"13S","DOI":"10.2967\/jnumed.121.263195","article-title":"The role of amyloid PET in imaging neurodegenerative disorders: a review","volume":"63","author":"Chapleau","year":"2022","journal-title":"J Nucl Med"},{"key":"2025040712175494600_ref7","doi-asserted-by":"crossref","first-page":"101496","DOI":"10.1016\/j.arr.2021.101496","article-title":"Past, present and future of therapeutic strategies against amyloid-beta peptides in Alzheimer's disease: a systematic review","volume":"72","author":"Jeremic","year":"2021","journal-title":"Ageing Res Rev"},{"key":"2025040712175494600_ref8","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20092161","article-title":"Targeting Apolipoprotein E for Alzheimer's disease: an industry perspective","volume":"20","author":"Suidan","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2025040712175494600_ref9","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/ana.21843","article-title":"APOE predicts amyloid-beta but not tau Alzheimer pathology in cognitively normal aging","volume":"67","author":"Morris","year":"2010","journal-title":"Ann Neurol"},{"key":"2025040712175494600_ref10","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/j.neurobiolaging.2010.04.007","article-title":"Amyloid imaging results from the Australian imaging, biomarkers and lifestyle (AIBL) study of aging","volume":"31","author":"Rowe","year":"2010","journal-title":"Neurobiol Aging"},{"key":"2025040712175494600_ref11","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s41591-024-02931-w","article-title":"APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease","volume":"30","author":"Fortea","year":"2024","journal-title":"Nat Med"},{"key":"2025040712175494600_ref12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cortex.2018.03.025","article-title":"APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: a review","volume":"104","author":"O'Donoghue","year":"2018","journal-title":"Cortex"},{"key":"2025040712175494600_ref13","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/j.1474-9726.2011.00705.x","article-title":"Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited","volume":"10","author":"Deelen","year":"2011","journal-title":"Aging Cell"},{"key":"2025040712175494600_ref14","doi-asserted-by":"crossref","first-page":"4420","DOI":"10.1093\/hmg\/ddu139","article-title":"Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age","volume":"23","author":"Deelen","year":"2014","journal-title":"Hum Mol Genet"},{"key":"2025040712175494600_ref15","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1212\/01.wnl.0000343853.00346.a4","article-title":"APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old","volume":"72","author":"Berlau","year":"2009","journal-title":"Neurology"},{"key":"2025040712175494600_ref16","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1001\/archneur.64.8.1193","article-title":"Dissociation of neuropathologic findings and cognition: case report of an apolipoprotein E epsilon2\/epsilon2 genotype","volume":"64","author":"Berlau","year":"2007","journal-title":"Arch Neurol"},{"key":"2025040712175494600_ref17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40478-023-01563-4","article-title":"Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease","volume":"11","author":"Ali","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"2025040712175494600_ref18","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","article-title":"New insights into the genetic etiology of Alzheimer's disease and related dementias","volume":"54","author":"Bellenguez","year":"2022","journal-title":"Nat Genet"},{"key":"2025040712175494600_ref19","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/ng.2892","article-title":"A general framework for estimating the relative pathogenicity of human genetic variants","volume":"46","author":"Kircher","year":"2014","journal-title":"Nat Genet"},{"key":"2025040712175494600_ref20","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The genotype-tissue expression (GTEx) project","volume":"45","author":"Consortium, G.T","year":"2013","journal-title":"Nat Genet"},{"key":"2025040712175494600_ref21","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nat Commun"},{"key":"2025040712175494600_ref22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41380-018-0246-7","article-title":"Genome-wide association study of brain amyloid deposition as measured by Pittsburgh compound-B (PiB)-PET imaging","volume":"26","author":"Yan","year":"2021","journal-title":"Mol Psychiatry"},{"key":"2025040712175494600_ref23","first-page":"647389","article-title":"Genetic interactions explain variance in cingulate amyloid burden: an AV-45 PET genome-wide association and interaction study in the ADNI cohort","volume":"2015","author":"Li","year":"2015","journal-title":"Biomed Res Int"},{"key":"2025040712175494600_ref24","doi-asserted-by":"crossref","first-page":"e0219668","DOI":"10.1371\/journal.pone.0219668","article-title":"The impact of APOE genotype on survival: results of 38,537 participants from six population-based cohorts (E2-CHARGE)","volume":"14","author":"Wolters","year":"2019","journal-title":"PLoS One"},{"key":"2025040712175494600_ref25","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s13024-020-00413-4","article-title":"APOE2: protective mechanism and therapeutic implications for Alzheimer's disease","volume":"15","author":"Li","year":"2020","journal-title":"Mol Neurodegener"},{"key":"2025040712175494600_ref26","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.neuron.2014.01.045","article-title":"ApoE and Abeta in Alzheimer's disease: accidental encounters or partners?","volume":"81","author":"Kanekiyo","year":"2014","journal-title":"Neuron"},{"key":"2025040712175494600_ref27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3233\/JAD-180802","article-title":"Understanding the amyloid hypothesis in Alzheimer's disease","volume":"68","author":"Paroni","year":"2019","journal-title":"J Alzheimers Dis"},{"key":"2025040712175494600_ref28","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.neuron.2017.11.013","article-title":"ApoE4 accelerates early seeding of amyloid pathology","volume":"96","author":"Liu","year":"2017","journal-title":"Neuron"},{"key":"2025040712175494600_ref29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13024-022-00574-4","article-title":"ApoE in Alzheimer's disease: pathophysiology and therapeutic strategies","volume":"17","author":"Raulin","year":"2022","journal-title":"Mol Neurodegener"},{"key":"2025040712175494600_ref30","doi-asserted-by":"crossref","first-page":"695479","DOI":"10.3389\/fncel.2021.695479","article-title":"Relationship between amyloid-beta deposition and blood-brain barrier dysfunction in Alzheimer's disease","volume":"15","author":"Wang","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"2025040712175494600_ref31","doi-asserted-by":"crossref","first-page":"1258640","DOI":"10.3389\/fnagi.2023.1258640","article-title":"Blood-brain barrier dysfunction and Alzheimer's disease: associations, pathogenic mechanisms, and therapeutic potential","volume":"15","author":"Chen","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"2025040712175494600_ref32","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.tem.2023.05.002","article-title":"Apolipoprotein E in lipid metabolism and neurodegenerative disease","volume":"34","author":"Yang","year":"2023","journal-title":"Trends Endocrinol Metab"},{"key":"2025040712175494600_ref33","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/s41588-018-0238-1","article-title":"Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer's disease susceptibility","volume":"50","author":"Raj","year":"2018","journal-title":"Nat Genet"},{"key":"2025040712175494600_ref34","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41467-020-20586-2","article-title":"Endophilin A2 deficiency protects rodents from autoimmune arthritis by modulating T cell activation","volume":"12","author":"Norin","year":"2021","journal-title":"Nat Commun"},{"key":"2025040712175494600_ref35","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/S1357-2725(02)00063-8","article-title":"Endophilin-1: a multifunctional protein","volume":"34","author":"Reutens","year":"2002","journal-title":"Int J Biochem Cell Biol"},{"key":"2025040712175494600_ref36","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/jb\/mvj120","article-title":"Physiological roles of clathrin adaptor AP complexes: lessons from mutant animals","volume":"139","author":"Ohno","year":"2006","journal-title":"J Biochem"},{"key":"2025040712175494600_ref37","doi-asserted-by":"crossref","first-page":"13267","DOI":"10.1096\/fj.201900909RR","article-title":"The role of Ap2a2 in PPARalpha-mediated regulation of lipolysis in adipose tissue","volume":"33","author":"Montgomery","year":"2019","journal-title":"FASEB J"},{"key":"2025040712175494600_ref38","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1038\/s41467-023-40208-x","article-title":"Compilation of reported protein changes in the brain in Alzheimer's disease","volume":"14","author":"Askenazi","year":"2023","journal-title":"Nat Commun"},{"key":"2025040712175494600_ref39","doi-asserted-by":"crossref","first-page":"e2204649","DOI":"10.1002\/advs.202204649","article-title":"Small molecular inhibitors reverse cancer metastasis by blockading oncogenic PITPNM3","volume":"9","author":"Liu","year":"2022","journal-title":"Adv Sci (Weinh)"},{"key":"2025040712175494600_ref40","doi-asserted-by":"crossref","first-page":"e12996","DOI":"10.1111\/bpa.12996","article-title":"Dysregulated protein phosphorylation: a determining condition in the continuum of brain aging and Alzheimer's disease","volume":"31","author":"Ferrer","year":"2021","journal-title":"Brain Pathol"},{"key":"2025040712175494600_ref41","doi-asserted-by":"crossref","first-page":"1190863","DOI":"10.3389\/fgene.2023.1190863","article-title":"Prioritization of risk genes for Alzheimer's disease: an analysis framework using spatial and temporal gene expression data in the human brain based on support vector machine","volume":"14","author":"Wang","year":"2023","journal-title":"Front Genet"},{"key":"2025040712175494600_ref42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.dadm.2016.12.003","article-title":"The effect of the top 20 Alzheimer disease risk genes on gray-matter density and FDG PET brain metabolism","volume":"5","author":"Stage","year":"2016","journal-title":"Alzheimers Dement (Amst)"},{"key":"2025040712175494600_ref43","doi-asserted-by":"crossref","first-page":"e258","DOI":"10.1212\/WNL.0000000000200351","article-title":"Brain metabolism and amyloid load in individuals with subjective cognitive decline or pre-mild cognitive impairment","volume":"99","author":"Tondo","year":"2022","journal-title":"Neurology"},{"key":"2025040712175494600_ref44","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1471-2121-14-32","article-title":"Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis","volume":"14","author":"Brentnall","year":"2013","journal-title":"BMC Cell Biol"},{"key":"2025040712175494600_ref45","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.jalz.2018.10.005","article-title":"A rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease","volume":"15","author":"Zhang","year":"2019","journal-title":"Alzheimers Dement"},{"key":"2025040712175494600_ref46","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1186\/s12877-022-03337-4","article-title":"TOMM40 genetic variants associated with healthy aging and longevity: a systematic review","volume":"22","author":"Chen","year":"2022","journal-title":"BMC Geriatr"},{"key":"2025040712175494600_ref47","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1007\/s11064-011-0459-5","article-title":"TOMM40 poly-T variants and cerebrospinal fluid amyloid beta levels in the elderly","volume":"36","author":"Pomara","year":"2011","journal-title":"Neurochem Res"},{"key":"2025040712175494600_ref48","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s12975-012-0161-1","article-title":"TOMM40 in cerebral amyloid Angiopathy related intracerebral Hemorrhage: comparative genetic analysis with Alzheimer's disease","volume":"3","author":"Valant","year":"2012","journal-title":"Transl Stroke Res"},{"key":"2025040712175494600_ref49","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.neurobiolaging.2021.12.013","article-title":"Association and interaction of TOMM40 and PVRL2 with plasma amyloid-beta and Alzheimer's disease among Chinese older adults: a population-based study","volume":"113","author":"Liang","year":"2022","journal-title":"Neurobiol Aging"},{"key":"2025040712175494600_ref50","doi-asserted-by":"crossref","first-page":"5469","DOI":"10.1007\/s00018-021-03854-2","article-title":"The Na(x) (SCN7A) channel: an atypical regulator of tissue homeostasis and disease","volume":"78","author":"Dolivo","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"2025040712175494600_ref51","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1080\/21678421.2020.1786128","article-title":"Concurrent sodium channelopathies and amyotrophic lateral sclerosis supports shared pathogenesis","volume":"21","author":"Franklin","year":"2020","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"2025040712175494600_ref52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2014.08.014","article-title":"Storm before the quiet: neuronal hyperactivity and Abeta in the presymptomatic stages of Alzheimer's disease","volume":"36","author":"Stargardt","year":"2015","journal-title":"Neurobiol Aging"},{"key":"2025040712175494600_ref53","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41593-018-0289-8","article-title":"Tau impairs neural circuits, dominating amyloid-beta effects, in Alzheimer models in vivo","volume":"22","author":"Busche","year":"2019","journal-title":"Nat Neurosci"},{"key":"2025040712175494600_ref54","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.neuron.2005.10.028","article-title":"Synaptic activity regulates interstitial fluid amyloid-beta levels in vivo","volume":"48","author":"Cirrito","year":"2005","journal-title":"Neuron"},{"key":"2025040712175494600_ref55","doi-asserted-by":"crossref","first-page":"e046129","DOI":"10.1002\/alz.046129","article-title":"Agora: an open platform for exploration of Alzheimer\u2019s disease evidence","volume":"16","author":"Greenwood","year":"2020","journal-title":"Alzheimers Dement"},{"key":"2025040712175494600_ref56","doi-asserted-by":"crossref","first-page":"e73377","DOI":"10.1371\/journal.pone.0073377","article-title":"Quantitative analysis of PiB-PET with FreeSurfer ROIs","volume":"8","author":"Su","year":"2013","journal-title":"PLoS One"},{"key":"2025040712175494600_ref57","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.neurobiolaging.2021.09.010","article-title":"Regional age-related atrophy after screening for preclinical alzheimer disease","volume":"109","author":"Koenig","year":"2022","journal-title":"Neurobiol Aging"},{"key":"2025040712175494600_ref58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jalz.2014.07.003","article-title":"The Centiloid project: standardizing quantitative amyloid plaque estimation by PET","volume":"11","author":"Klunk","year":"2015","journal-title":"Alzheimers Dement"},{"key":"2025040712175494600_ref59","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"2025040712175494600_ref60","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"2025040712175494600_ref61","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13073-020-00803-9","article-title":"dbNSFP v4: a comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs","volume":"12","author":"Liu","year":"2020","journal-title":"Genome Med"},{"key":"2025040712175494600_ref62","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/humu.24309","article-title":"Variant interpretation using population databases: lessons from gnomAD","volume":"43","author":"Gudmundsson","year":"2022","journal-title":"Hum Mutat"},{"key":"2025040712175494600_ref63","doi-asserted-by":"crossref","first-page":"D840","DOI":"10.1093\/nar\/gkw971","article-title":"The ExAC browser: displaying reference data information from over 60 000 exomes","volume":"45","author":"Karczewski","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2025040712175494600_ref64","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Genomes Project, C","year":"2015","journal-title":"Nature"},{"key":"2025040712175494600_ref65","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2025040712175494600_ref66","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.ajhg.2013.04.015","article-title":"Sequence kernel association tests for the combined effect of rare and common variants","volume":"92","author":"Ionita-Laza","year":"2013","journal-title":"Am J Hum Genet"},{"key":"2025040712175494600_ref67","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/8\/739\/61817529\/ddaf017.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/34\/8\/739\/61817529\/ddaf017.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T15:26:36Z","timestamp":1744039596000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/34\/8\/739\/8006252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":67,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,2,10]]},"published-print":{"date-parts":[[2025,4,6]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddaf017","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4,15]]},"published":{"date-parts":[[2025,2,10]]}}}