{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T19:56:23Z","timestamp":1792871783977,"version":"4.5.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010805","name":"Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    We reviewed the literature on sex differences in genetically determined Alzheimer\u2019s disease (AD), focusing on autosomal dominant AD (ADAD), Down syndrome-associated AD (DSAD), and\n                    <jats:italic>APOE4<\/jats:italic>\n                    homozygosity, particularly regarding disease penetrance, symptom onset and clinical progression, and trajectories for markers of amyloidosis (A), tau pathology (T) and neurodegeneration (N). Data suggests that sex differences in disease penetrance, symptom onset, and AT(N) biomarker trajectories are typically subtle for genetically determined AD populations. Noteworthy exceptions, such as increased neurodegeneration in later stages of the disease in females while similar cognitive outcomes, suggest a potential differential cognitive reserve that warrants further investigation. Additionally, the interaction between\n                    <jats:italic>APOE<\/jats:italic>\n                    genotype and sex reveals complex and multifaceted effects in DSAD, with potential implications for ADAD that remain underexplored. The smaller sex differences observed compared to sporadic AD offer insights into the different underlying disease mechanisms in genetically determined AD populations. Future research should prioritize sex-specific investigations in genetically determined AD, focusing on refining methodologies. This includes prioritizing longitudinal designs, adjustment for key confounders, and adherence to sex-specific guidelines.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2025.1522434","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T02:10:00Z","timestamp":1741054200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Sex-related differences in genetically determined Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Laura","family":"Del Hoyo Soriano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Wagemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Bejanin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Levin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1001\/jamaneurol.2015.4851","article-title":"Cognitive decline in a Colombian kindred with autosomal dominant Alzheimer disease a retrospective cohort study","volume":"73","author":"Aguirre-Acevedo","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.1002\/ALZ.13809","article-title":"Alzheimer\u2019s Disease Facts and Figures","volume":"20","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"10491","DOI":"10.1038\/s41598-020-67195-z","article-title":"Plasma metabolome and cognitive skills in down syndrome","volume":"10","author":"Antonaros","year":"2020","journal-title":"Sci. Rep."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"5695","DOI":"10.1002\/ALZ.13844","article-title":"Sex and gender differences in cognitive resilience to aging and Alzheimer\u2019s disease","volume":"20","author":"Arenaza-Urquijo","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1038\/S41467-020-14959-W","article-title":"Sex and APOE \u03b54 genotype modify the Alzheimer\u2019s disease serum metabolome","volume":"11","author":"Arnold","year":"2020","journal-title":"Nat Commun."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1056\/NEJMoa1202753","article-title":"Clinical and biomarker changes in dominantly inherited Alzheimer\u2019s disease","volume":"367","author":"Bateman","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1001\/jamaneurol.2021.1893","article-title":"Association of Apolipoprotein E \u03b54 allele with clinical and multimodal biomarker changes of Alzheimer disease in adults with down syndrome supplemental content","volume":"78","author":"Bejanin","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1001\/JAMANEUROL.2023.3599","article-title":"APOE genotype and Alzheimer disease risk across age, sex, and population ancestry","volume":"80","author":"Belloy","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3719","DOI":"10.1093\/BRAIN\/AWAD100","article-title":"Determinants of cognitive and brain resilience to tau pathology: a longitudinal analysis","volume":"146","author":"Bocancea","year":"2023","journal-title":"Brain"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1001\/JAMANEUROL.2019.1534","article-title":"Diagnostic value of cerebrospinal fluid Neurofilament light protein in neurology: A systematic review and Meta-analysis","volume":"76","author":"Bridel","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1001\/JAMANEUROL.2018.4693","article-title":"Sex differences in the Association of Global Amyloid and Regional tau Deposition Measured by positron emission tomography in clinically Normal older adults","volume":"76","author":"Buckley","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/J.NEUROBIOLAGING.2019.05.023","article-title":"Identification of age- and gender-associated long noncoding RNAs in the human brain with Alzheimer\u2019s disease","volume":"81","author":"Cao","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1002\/DNEU.22709","article-title":"Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: the complex triangle of brain amyloidosis","volume":"79","author":"Carmona-Iragui","year":"2019","journal-title":"Dev. Neurobiol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1105620","DOI":"10.3389\/fnagi.2023.1105620","article-title":"Sex and gender considerations in Alzheimer\u2019s disease: the Women\u2019s brain project contribution","volume":"15","author":"Castro-Aldrete","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/J.JALZ.2013.10.005","article-title":"Gender and incidence of dementia in the Framingham heart study from mid-adult life","volume":"11","author":"Ch\u00eane","year":"2015","journal-title":"Alzheimers Dement."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"708","DOI":"10.3389\/fpsyg.2015.00708","article-title":"A new cognitive evaluation battery for down syndrome and its relevance for clinical trials","volume":"6","author":"de Sola","year":"2015","journal-title":"Front. Psychol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13293-022-00448-w","article-title":"Sex differences in the human brain: a roadmap for more careful analysis and interpretation of a biological reality","volume":"13","author":"DeCasien","year":"2022","journal-title":"Biol. Sex Differ."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3389\/fgene.2018.00424","article-title":"Specificity: A phenotypic comparison of communication-relevant domains between youth with down syndrome and fragile X syndrome","volume":"9","author":"del Hoyo Soriano","year":"2018","journal-title":"Front. Genet."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1007\/S00401-018-1881-4","article-title":"Sex-specific genetic predictors of Alzheimer\u2019s disease biomarkers","volume":"136","author":"Deming","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref20","first-page":"757","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: the IWG-2 criteria","volume-title":"Lancet Neurol.","author":"Dubois","year":"2014"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1002\/AJMG.C.31865","article-title":"Autosomal dominant early onset Alzheimer\u2019s disease in the Mexican state of Jalisco: high frequency of the mutation PSEN1 c.1292C>A and phenotypic profile of patients","volume":"184","author":"Dumois-Petersen","year":"2020","journal-title":"Am. J. Med. Genet. C: Semin. Med. Genet."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/J.NEUBIOREV.2021.02.026","article-title":"Dump the \u201cdimorphism\u201d: comprehensive synthesis of human brain studies reveals few male-female differences beyond size","volume":"125","author":"Eliot","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1001\/JAMA.1997.03550160069041","article-title":"Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A Meta-analysis","volume":"278","author":"Farrer","year":"1997","journal-title":"JAMA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41582-018-0032-9","article-title":"Sex differences in Alzheimer disease \u2014 the gateway to precision medicine","volume":"14","author":"Ferretti","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/s41591-024-02931-w","article-title":"APOE4 homozygosity represents a distinct genetic form of Alzheimer\u2019s disease","volume":"30","author":"Fortea","year":"2024","journal-title":"Nat. Med."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1016\/S0140-6736(20)30689-9","article-title":"Clinical and biomarker changes of Alzheimer\u2019s disease in adults with down syndrome: a cross-sectional study","volume":"395","author":"Fortea","year":"2020","journal-title":"Lancet"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/S1474-4422(21)00245-3","article-title":"Alzheimer\u2019s disease associated with down syndrome: a genetic form of dementia","volume":"20","author":"Fortea","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"E2121697","DOI":"10.1001\/JAMANETWORKOPEN.2021.21697","article-title":"Sex differences in cognitive abilities among children with the autosomal dominant Alzheimer disease Presenilin 1 E280A variant from a Colombian cohort","volume":"4","author":"Fox-Fuller","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1002\/ALZ.13506","article-title":"Alzheimer\u2019s polygenic risk scores are associated with cognitive phenotypes in down syndrome","volume":"20","author":"Gorijala","year":"2024","journal-title":"Alzheimers Dementia"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/J.BIOPSYCH.2021.02.968","article-title":"Sex differences in Alzheimer\u2019s disease: insights from the multiomics landscape","volume":"91","author":"Guo","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/ALZ.12694","article-title":"Global estimates on the number of persons across the Alzheimer\u2019s disease continuum","volume":"19","author":"Gustavsson","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"e12096","DOI":"10.1002\/DAD2.12096","article-title":"Cognitive indicators of transition to preclinical and prodromal stages of Alzheimer\u2019s disease in down syndrome","volume":"12","author":"Hartley","year":"2020","journal-title":"Alzheimers Dementia"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1177\/17456916221082116","article-title":"Sex\/gender differences in verbal fluency and verbal-episodic memory: A Meta-analysis","volume":"18","author":"Hirnstein","year":"2023","journal-title":"Perspect. Psychol. Sci."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.3233\/JAD-220724","article-title":"Could country-level factors explain sex differences in dementia incidence and prevalence? A systematic review and Meta-analysis","volume":"91","author":"Huque","year":"2023","journal-title":"J. Alzheimers Disease"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"fcad074","DOI":"10.1093\/BRAINCOMMS\/FCAD074","article-title":"Association of biological sex with clinical outcomes and biomarkers of Alzheimer\u2019s disease in adults with down syndrome","volume":"5","author":"Iulita","year":"2023","journal-title":"Brain Commun."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e2212910","DOI":"10.1001\/JAMANETWORKOPEN.2022.12910","article-title":"Association of Alzheimer Disease with Life Expectancy in people with down syndrome","volume":"5","author":"Iulita","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1001\/JAMANEUROL.2021.5216","article-title":"Prevalence estimates of amyloid abnormality across the Alzheimer disease clinical Spectrum","volume":"79","author":"Jansen","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1001\/JAMA.2015.4668","article-title":"Prevalence of cerebral amyloid pathology in persons without dementia: A Meta-analysis","volume":"313","author":"Jansen","year":"2015","journal-title":"JAMA"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1038\/s41591-023-02476-4","article-title":"Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer\u2019s disease","volume":"29","author":"Johnson","year":"2023","journal-title":"Nat. Med."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"e33008","DOI":"10.1002\/AJMG.B.33008","article-title":"Sex differences in cortical thickness and neuropsychiatric symptom burden based on APOE4 homozygosity in Alzheimer\u2019s disease","volume":"198","author":"Khoury","year":"2024","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"fcab088","DOI":"10.1093\/BRAINCOMMS\/FCAB088","article-title":"High resolution structural and functional MRI of the hippocampus in young adults with down syndrome","volume":"3","author":"Koenig","year":"2021","journal-title":"Brain Commun."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41398-023-02411-8","article-title":"Sex difference in evolution of cognitive decline: studies on mouse model and the dominantly inherited Alzheimer network cohort","volume":"13","author":"Kommaddi","year":"2023","journal-title":"Transl. Psychiatry."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1212\/WNL.53.2.331","article-title":"APOE genotype and gender effects on Alzheimer disease in 100 adults with down syndrome","volume":"53","author":"Lai","year":"1999","journal-title":"Neurology"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e12084","DOI":"10.1002\/DAD2.12084","article-title":"Sex differences in risk of Alzheimer\u2019s disease in adults with down syndrome","volume":"12","author":"Lai","year":"2020","journal-title":"Alzheimers Dementia"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1186\/S13195-024-01572-Y","article-title":"Impact of APOE \u03b54 and \u03b52 on plasma neurofilament light chain and cognition in autosomal dominant Alzheimer\u2019s disease","volume":"16","author":"Langella","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"5120","DOI":"10.1038\/s41467-023-40775-z","article-title":"Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer\u2019s disease","volume":"14","author":"Langella","year":"2023","journal-title":"Nat. Commun."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e1002270","DOI":"10.1371\/JOURNAL.PMED.1002270","article-title":"APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases","volume":"14","author":"Lanoisel\u00e9e","year":"2017","journal-title":"PLoS Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1002\/ALZ.13779","article-title":"Age of Alzheimer\u2019s disease diagnosis in people with down syndrome and associated factors: results from the horizon 21 European down syndrome consortium","volume":"20","author":"Larsen","year":"2024","journal-title":"Alzheimers Dementia"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1037\/BUL0000191","article-title":"The development of gender differences in spatial reasoning: a meta-analytic review","volume":"145","author":"Lauer","year":"2019","journal-title":"Psychol. Bull."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1002\/wcs.1380","article-title":"Sex differences in spatial cognition: advancing the conversation","volume":"7","author":"Levine","year":"2016","journal-title":"Wiley Interdiscip. Rev. Cogn. Sci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1007\/S00401-018-1908-X","article-title":"Sex and age interact to determine clinicopathologic differences in Alzheimer\u2019s disease","volume":"136","author":"Liesinger","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/J.TRCI.2015.07.001","article-title":"Marked gender differences in progression of mild cognitive impairment over 8 years","volume":"1","author":"Lin","year":"2015","journal-title":"Alzheimers Dementia"},{"key":"ref94","doi-asserted-by":"publisher","first-page":"4959","DOI":"10.7150\/thno.35366","article-title":"Sex modulates the ApoE \u03b54 effect on brain tau deposition measured by 18F-AV-1451 PET in individuals with mild cognitive impairment","volume":"9","author":"Liu","year":"2022","journal-title":"Theranostics"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"E9645","DOI":"10.1073\/PNAS.1707151114","article-title":"Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer\u2019s disease","volume":"114","author":"Mano","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s00401-025-02844-z","article-title":"Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer\u2019s disease, and late-onset Alzheimer\u2019s disease","volume":"149","author":"Mart\u00e1-Ariza","year":"2025","journal-title":"Acta Neuropathol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/S41586-019-1195-2","article-title":"Single-cell transcriptomic analysis of Alzheimer\u2019s disease","volume":"570","author":"Mathys","year":"2019","journal-title":"Nature"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.3390\/JCM10132966","article-title":"The association between sex and risk of Alzheimer\u2019s disease in adults with down syndrome","volume":"10","author":"Mhatre","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1373\/JALM.2019.030023","article-title":"Consideration of sex differences in the measurement and interpretation of Alzheimer disease-related biofluid-based biomarkers","volume":"5","author":"Mielke","year":"2020","journal-title":"J. Appl. Lab. Med."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2147\/CLEP.S37929","article-title":"Clinical epidemiology of Alzheimer\u2019s disease: assessing sex and gender differences","volume":"6","author":"Mielke","year":"2014","journal-title":"Clin. Epidemiol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/S13024-023-00688-3\/FIGURES\/5","article-title":"Advanced structural brain aging in preclinical autosomal dominant Alzheimer disease","volume":"18","author":"Millar","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"2704","DOI":"10.1038\/S41588-024-01961-X","article-title":"Spatial and single-nucleus transcriptomic analysis of genetic and sporadic forms of Alzheimer\u2019s disease","volume":"56","author":"Miyoshi","year":"2024","journal-title":"Nat. Genet."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2174\/156720512801322546","article-title":"The Nun study: risk factors for pathology and clinical-pathologic correlations","volume":"9","author":"Mortimer","year":"2013","journal-title":"Curr. Alzheimer Res."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"735611","DOI":"10.3389\/fnagi.2021.735611","article-title":"Sex-specific cross tissue Meta-analysis identifies immune dysregulation in women with Alzheimer\u2019s disease","volume":"13","author":"Paranjpe","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/ANA.10636","article-title":"Apolipoprotein Eepsilon4 modifies Alzheimer\u2019s disease onset in an E280A PS1 kindred","volume":"54","author":"Pastor","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"919711","DOI":"10.3389\/FNINT.2022.919711","article-title":"Physical activity, memory function, and hippocampal volume in adults with down syndrome","volume":"16","author":"Peven","year":"2022","journal-title":"Front. Integr. Neurosci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1002\/GPS.2039","article-title":"Significant effect of APOE epsilon 4 genotype on the risk of dementia in Alzheimer\u2019s disease and mortality in persons with down syndrome","volume":"23","author":"Prasher","year":"2008","journal-title":"Int. J. Geriatr. Psychiatry"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1056\/NEJMOA2308583","article-title":"APOE3 Christchurch heterozygosity and autosomal dominant Alzheimer\u2019s disease","volume":"390","author":"Quiroz","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"e39904","DOI":"10.1371\/JOURNAL.PONE.0039904","article-title":"Gender, culture, and sex-typed cognitive abilities","volume":"7","author":"Reilly","year":"2012","journal-title":"PLoS One"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-024-47261-0","article-title":"Impression management in sex and gender neuroscience research reporting: the MAGIC guidelines","volume":"15","author":"Rippon","year":"2024","journal-title":"Nat. Commun."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/S00234-014-1482-4","article-title":"Age effects on cortical thickness in young Down\u2019s syndrome subjects: a cross-sectional gender study","volume":"57","author":"Romano","year":"2015","journal-title":"Neuroradiology"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1001\/JAMANEUROL.2019.3666","article-title":"Epidemiology of dementia and Alzheimer disease in individuals with down syndrome","volume":"77","author":"Rubenstein","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref72","article-title":"Alzheimer\u2019s disease in a full Medicaid and Medicare sample of US adults with down syndrome","volume-title":"Poster presented at the 5th international conference of the trisomy 21 research society","author":"Rubenstein","year":"2024"},{"key":"ref73","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1212\/WNL.0000000000000596","article-title":"Symptom onset in autosomal dominant Alzheimer disease: A systematic review and meta-analysis","volume":"83","author":"Ryman","year":"2014","journal-title":"Neurology"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"bhae067","DOI":"10.1093\/CERCOR\/BHAE067","article-title":"Cortical thickness reveals sex differences in verbal and visuospatial memory","volume":"34","author":"Sang","year":"2024","journal-title":"Cerebral Cortex"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1212\/WNL.50.4.991","article-title":"Earlier onset of Alzheimer\u2019s disease in men with down syndrome","volume":"50","author":"Schupf","year":"1998","journal-title":"Neurology"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"e0225392","DOI":"10.1371\/JOURNAL.PONE.0225392","article-title":"Evidence in support of chromosomal sex influencing plasma based metabolome vs APOE genotype influencing brain metabolome profile in humanized APOE male and female mice","volume":"15","author":"Shang","year":"2020","journal-title":"PLoS One"},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e211001","DOI":"10.1001\/JAMANETWORKOPEN.2021.1001","article-title":"Evaluation of selective survival and sex\/gender differences in dementia incidence using a simulation model","volume":"4","author":"Shaw","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"e69124","DOI":"10.7759\/CUREUS.69124","article-title":"Influence of the onset of menopause on the risk of developing Alzheimer\u2019s disease","volume":"16","author":"Silva","year":"2024","journal-title":"Cureus"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/JPPI.12042","article-title":"Intellectual disability, mild cognitive impairment, and risk for dementia","volume":"10","author":"Silverman","year":"2013","journal-title":"J. Policy Pract. Intellect. Disabil."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"7490","DOI":"10.1038\/S41598-018-25377-W","article-title":"Sex differences in cognitive decline in subjects with high likelihood of mild cognitive impairment due to Alzheimer\u2019s disease","volume":"8","author":"Sohn","year":"2018","journal-title":"Sci. Rep."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1016\/J.SOCSCIMED.2012.03.001","article-title":"Gender and health: relational, intersectional, and biosocial approaches","volume":"74","author":"Springer","year":"2012","journal-title":"Soc. Sci. Med."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s11689-019-9306-9","article-title":"Health comorbidities and cognitive abilities across the lifespan in down syndrome","volume":"12","author":"Startin","year":"2020","journal-title":"J. Neurodev. Disord."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1001\/JAMA.279.10.751","article-title":"The APOE-\u220a4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics","volume":"279","author":"Tang","year":"1998","journal-title":"JAMA"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"E975","DOI":"10.1212\/WNL.0000000000011416\/ASSET\/425395AF-DD29-4E3B-B419-D54D4A386573\/ASSETS\/GRAPHIC\/5TTU1.GIF","article-title":"Frequency of biologically defined Alzheimer disease in relation to age, sex, APOE \u03f54, and cognitive impairment","volume":"96","author":"Therriault","year":"2021","journal-title":"Neurology"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"4314","DOI":"10.1038\/S41380-022-01675-8","article-title":"Sex differences in plasma p-tau181 associations with Alzheimer\u2019s disease biomarkers, cognitive decline, and clinical progression","volume":"27","author":"Tsiknia","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"15687","DOI":"10.3390\/IJMS242115687","article-title":"Potential modifying effect of the APOE\u03b54 allele on age of onset and clinical manifestations in patients with early-onset Alzheimer\u2019s disease with and without a pathogenic variant in PSEN1 in a sample of the Mexican population","volume":"24","author":"Valdez-Gaxiola","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"4495","DOI":"10.1093\/BRAIN\/AWAD213","article-title":"CSF proteomics in autosomal dominant Alzheimer\u2019s disease highlights parallels with sporadic disease","volume":"146","author":"Van Der Ende","year":"2023","journal-title":"Brain"},{"key":"ref88","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/MP.2015.177","article-title":"APOE*E2 allele delays age of onset in PSEN1 E280A Alzheimer\u2019s disease","volume":"21","author":"V\u00e9lez","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref89","doi-asserted-by":"publisher","first-page":"4127","DOI":"10.1002\/ALZ.13314","article-title":"Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer\u2019s disease","volume":"19","author":"Vila-Castelar","year":"2023","journal-title":"Alzheimers Dement."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.3233\/JAD-200723","article-title":"Examining sex differences in markers of cognition and neurodegeneration in autosomal dominant Alzheimer\u2019s disease: preliminary findings from the Colombian Alzheimer\u2019s prevention initiative biomarker study","volume":"77","author":"Vila-Castelar","year":"2020","journal-title":"J. Alzheimers Disease"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1002\/ALZ.12552","article-title":"Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer\u2019s disease carriers and non-carriers: baseline findings from the API ADAD Colombia trial","volume":"18","author":"Vila-Castelar","year":"2022","journal-title":"Alzheimers Dement."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1002\/ALZ.13460","article-title":"Investigation of sex differences in mutation carriers of the dominantly inherited Alzheimer network","volume":"20","author":"Wagemann","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1001\/JAMANEUROL.2023.2169","article-title":"Associations of sex, race, and apolipoprotein E alleles with multiple domains of cognition among older adults","volume":"80","author":"Walters","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"3201","DOI":"10.1093\/BRAIN\/AWAB160","article-title":"Sex modifies APOE \u03b54 dose effect on brain tau deposition in cognitively impaired individuals","volume":"144","author":"Yan","year":"2021","journal-title":"Brain"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"01.626234","DOI":"10.1101\/2024.12.01.626234","article-title":"The landscape of sex- and APOE genotype-specific transcriptional changes in Alzheimer\u2019s disease at the single cell level","volume":"2024","author":"Yu","year":"2024","journal-title":"BioRxiv"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"4907","DOI":"10.1007\/S00018-021-03830-W","article-title":"Alzheimer\u2019s pathogenic mechanisms and underlying sex difference","volume":"78","author":"Zhu","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"886","DOI":"10.14283\/JPAD.2023.115","article-title":"Genotypic effects of the TOMM40\u2019523 variant and APOE on longitudinal cognitive change over 4 years: the TOMMORROW study","volume":"10","author":"Zou","year":"2023","journal-title":"J. Prev Alzheimers Dis."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1522434\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T02:10:04Z","timestamp":1741054204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1522434\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":97,"alternative-id":["10.3389\/fnagi.2025.1522434"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2025.1522434","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"article-number":"1522434"}}