{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T19:14:30Z","timestamp":1773688470826,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Education of the Junta de Castilla &amp; Le\u00f3n","award":["067\/230003"],"award-info":[{"award-number":["067\/230003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Alzheimer\u2019s dementia is a progressive neurodegenerative disease that affects memory abilities due to genetic and environmental factors. A well-known gene that influences the risk of Alzheimer\u2019s disease is the apolipoprotein E (APOE) gene. The APOE gene is involved in the production of a protein that helps transport cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer\u2019s disease. APOE comes in several forms, which are called alleles (\u03b52, \u03b53, \u03b54). Materials and Methods: Therefore, our study aims to identify those subjects with a higher genetic risk through the polymorphism of the APOE gene, using a population screening in patients with a clinical diagnosis of AD in a region of Spain, Castilla y Le\u00f3n, as potential biomarkers and to identify individuals at increased genetic risk by polymorphism of the APOE gene. An observational case-control study was conducted in Castilla y Le\u00f3n (Spain). Saliva samples were collected and the ApoE gene was analyzed by PCR and agarose gel electrophoresis, respecting ethical criteria. Results: In the Alzheimer\u2019s population in Castilla y Le\u00f3n, a high prevalence of ApoE3 (74%) was found, followed by ApoE4 (22%); in addition, a higher presence of the \u03b54 allele was found in the Alzheimer\u2019s disease (AD) group than in the control group. It was also observed that the \u03b52\/\u03b52 genotype was not found in any individual with AD but was found in healthy subjects and that the opposite was observed for the \u03b54\/\u03b54 genotype. The odds ratio (OR) indicated a risk four times greater of having AD if having the \u03b54 allele. Conclusions: The demonstrated relation between the different isoforms and the likelihood of developing AD has led to its consideration as a biomarker and a potential pre-symptomatic therapy. The molecular mechanisms that confer a disruptive and protective role to ApoE4 and ApoE2, respectively, are still being studied.<\/jats:p>","DOI":"10.3390\/medicina60121941","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:25:19Z","timestamp":1732515919000},"page":"1941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prevalence of ApoE Alleles in a Spanish Population of Patients with a Clinical Diagnosis of Alzheimer\u2019s Disease: An Observational Case-Control Study"],"prefix":"10.3390","volume":"60","author":[{"given":"Laura","family":"Bello-Corral","sequence":"first","affiliation":[{"name":"Health Research Nursing Group (GREIS), University of Leon, 24071 Leon, Spain"},{"name":"Department of Nursing and Physiotherapy, University of Leon, 24071 Leon, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-9777","authenticated-orcid":false,"given":"Jes\u00fas","family":"Seco-Calvo","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Le\u00f3n, 24071 Leon, Spain"},{"name":"Department of Physiology, University of the Basque Country, 48940 Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5684-9406","authenticated-orcid":false,"given":"Angela","family":"Molina Fresno","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, Rovira i Virgili University, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Isabel","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Genetics Area, Department of Molecular Biology, University of Le\u00f3n, 24071 Leon, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Llorente","sequence":"additional","affiliation":[{"name":"Genetics Area, Department of Molecular Biology, University of Le\u00f3n, 24071 Leon, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6522-8896","authenticated-orcid":false,"given":"Diego","family":"Fern\u00e1ndez-L\u00e1zaro","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology, Genetics, Histology and Pharmacology, Faculty of Health Sciences, University of Valladolid, Campus of Soria, 42004 Soria, Spain"},{"name":"Neurobiology Research Group, Faculty of Medicine, University of Valladolid, 47002 Valladolid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-4644","authenticated-orcid":false,"given":"Leticia","family":"S\u00e1nchez-Valde\u00f3n","sequence":"additional","affiliation":[{"name":"Health Research Nursing Group (GREIS), University of Leon, 24071 Leon, Spain"},{"name":"Department of Nursing and Physiotherapy, University of Leon, 24071 Leon, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,25]]},"reference":[{"key":"ref_1","first-page":"4338","article-title":"Enfermedad de Alzheimer","volume":"12","author":"Soldevilla","year":"2019","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jocn.2015.12.032","article-title":"Professor Alois Alzheimer (1864\u20131915): Lest we forget","volume":"31","author":"Toodayan","year":"2016","journal-title":"J. Clin. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s40120-022-00338-8","article-title":"Alzheimer\u2019s disease: Epidemiology and clinical progression","volume":"11","author":"Byrnes","year":"2022","journal-title":"Neurol. Ther."},{"key":"ref_4","first-page":"371","article-title":"Diagnosis of Early Alzheimer\u2019s Disease: Clinical Practice in 2021","volume":"8","author":"Porsteinsson","year":"2021","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Breijyeh, Z., and Karaman, R. (2020). Comprehensive Review on Alzheimer\u2019s Disease: Causes and Treatment. Molecules, 25.","DOI":"10.3390\/molecules25245789"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1523\/JNEUROSCI.4315-03.2004","article-title":"Neuron-specific apolipoprotein e4 proteolysis is associated with increased tau phosphorylation in brains of transgenic mice","volume":"24","author":"Brecht","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/B978-0-12-804766-8.00013-3","article-title":"Alzheimer\u2019s disease","volume":"167","year":"2019","journal-title":"Handb. Clin. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jalz.2016.02.010","article-title":"Neuroinflammation in Alzheimer\u2019s disease: Current evidence and future directions","volume":"12","author":"Calsolaro","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_9","first-page":"892","article-title":"Genetic of Alzheimer\u2019s Disease: A Narrative Review Article","volume":"44","author":"Khanahmadi","year":"2015","journal-title":"Iran. J. Public Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.bcp.2013.12.024","article-title":"Alzheimer disease: Epidemiology, diagnostic criteria, risk factors and biomarkers","volume":"88","author":"Reitz","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jalz.2016.02.002","article-title":"Preclinical Alzheimer\u2019s disease: Definition, natural history, and diagnostic criteria","volume":"12","author":"Dubois","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1016\/S0021-9258(18)88963-3","article-title":"Isolation, characterization, and mapping to chromosome 19 of the human apolipoprotein E gene","volume":"260","author":"Das","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_13","first-page":"363","article-title":"Apolipoprotein E polymorphism in cerebrovascular & coronary heart diseases","volume":"132","author":"Anoop","year":"2010","journal-title":"Indian J. Med. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The role of apolipoprotein E in Alzheimer\u2019s disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.nbd.2014.08.025","article-title":"Apolipoprotein E: Structure and function in lipid metabolism, neurobiology, and Alzheimer\u2019s diseases","volume":"72","author":"Huang","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/0958-1669(94)90091-4","article-title":"APOE is a major susceptibility gene for Alzheimer\u2019s disease","volume":"5","author":"Roses","year":"1994","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_17","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":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neurobiolaging.2012.04.017","article-title":"Apolipoprotein E \u03b54 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease","volume":"34","author":"Fleisher","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/mp.2010.57","article-title":"Molecular signatures in post-mortem brain tissue of younger individuals at high risk for Alzheimer\u2019s disease as based on APOE genotype","volume":"16","author":"Hyde","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1073\/pnas.061509598","article-title":"Declining brain activity in cognitively normal apolipoprotein E 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer\u2019s disease","volume":"98","author":"Reiman","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1373\/clinchem.2003.021683","article-title":"Simple Sequence-specific-Primer-PCR Method To Identify the Three Main Apolipoprotein E Haplotypes","volume":"49","author":"Pantelidis","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Papastefanopoulou, V., Stanitsa, E., Koros, C., Simoudis, A., Florou-Hatziyiannidou, C., Beratis, I., Antonelou, R., Andronas, N., Voskou, P., and Angelopoulou, E. (2023). ApoE allele frequency in Southern Greece: Exploring the role of geographical gradient in the Greek population. Geriatrics, 8.","DOI":"10.3390\/geriatrics8010001"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1097\/00001756-200303240-00016","article-title":"Apolipoprotein E (ApoE) polymorphism influences serum ApoE levels in Alzheimer\u2019s disease patients and centenarians","volume":"14","author":"Panza","year":"2003","journal-title":"Neuroreport"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, R.D., Gomes, I., Gomes, C., Rocha, R., Dur\u00e3es, L., Sousa, P., Figueruelo, M., Rodr\u00edguez, M., Pita, C., and Hornero, R. (2021). Apoe variants in an Iberian Alzheimer cohort detected through an optimized sanger sequencing protocol. Genes, 12.","DOI":"10.3390\/genes12010004"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0304-3940(94)90867-2","article-title":"Apolipoprotein E e4 allele frequency in patients with Lewy body dementia, Alzheimer\u2019s disease and age-matched controls","volume":"176","author":"Clair","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000106637","article-title":"Apolipoprotein-E genotyping in Alzheimer\u2019s disease and Frontotemporal dementia","volume":"8","author":"Gustafson","year":"1997","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.55782\/ane-1998-1260","article-title":"ApoE polymorphism in Polish patients with Alzheimer\u2019s disease","volume":"58","author":"Lalowski","year":"1998","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1469-1809.1995.tb00741.x","article-title":"Apolipoprotein E polymorphism in Italy investigated in native plasma by a simple polyacrylamide gel isoelectric focusing technique. Comparison with frequency data of other European populations","volume":"59","author":"Corb","year":"1995","journal-title":"Ann. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/0022-510X(95)00238-3","article-title":"Apolipoprotein E genotype in Spanish patients of Alzheimer\u2019s or Parkinson\u2019s disease","volume":"134","author":"Ibarreta","year":"1995","journal-title":"J. Neurol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/s41467-018-08272-w","article-title":"Patterns of genetic differentiation and the footprints of historical migrations in the Iberian Peninsula","volume":"10","author":"Bycroft","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0304-3940(96)12415-0","article-title":"Apolipoprotein E polymorphism and susceptibility to early-and late-onset sporadic Alzheimer\u2019s disease in Hokkaido, the northern part of Japan","volume":"206","author":"Nunomura","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.5377\/creaciencia.v13i2.11757","article-title":"Apolipoprote\u00edna \u00e9psilon cuatro y enfermedad de alzheimer en pacientes del instituto salvadore\u00f1o del seguro social","volume":"13","year":"2021","journal-title":"Crea Cienc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89ra57","DOI":"10.1126\/scitranslmed.3002156","article-title":"Human apoE isoforms differentially regulate brain amyloid-\u03b2 peptide clearance","volume":"3","author":"Castellano","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"212ra161","DOI":"10.1126\/scitranslmed.3007000","article-title":"Gene transfer of human Apoe isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain","volume":"5","author":"Hudry","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11445","DOI":"10.1523\/JNEUROSCI.1972-08.2008","article-title":"Impact of apolipoprotein E (ApoE) polymorphism on brain ApoE levels","volume":"28","author":"Riddell","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10571","DOI":"10.1021\/bi9626362","article-title":"Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide beta (1\u201340). Relevance to Alzheimer\u2019s disease","volume":"36","author":"Aleshkov","year":"1997","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4002","DOI":"10.1172\/JCI36663","article-title":"apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain","volume":"118","author":"Deane","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cell.2016.12.044","article-title":"ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and A\u03b2 Secretion","volume":"168","author":"Huang","year":"2017","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/mp.2013.194","article-title":"APOE2 enhances neuroprotection against Alzheimer\u2019s disease through multiple molecular mechanisms","volume":"19","author":"Gomar","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8838","DOI":"10.1073\/pnas.151254698","article-title":"Apolipoprotein E fragments present in Alzheimer\u2019s disease brains induce neurofibrillary tangle-like intracellular inclusions in neurons","volume":"98","author":"Huang","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10966","DOI":"10.1073\/pnas.1434398100","article-title":"Carboxyl-terminal-truncated apolipoprotein E4 causes Alzheimer\u2019s disease-like neurodegeneration and behavioral deficits in transgenic mice","volume":"100","author":"Harris","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/00001756-200205070-00026","article-title":"Truncated apoE forms tangle-like structures in a neuronal cell line","volume":"13","author":"Ljungberg","year":"2002","journal-title":"Neuroreport"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11183","DOI":"10.1073\/pnas.91.23.11183","article-title":"Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: Implications for Alzheimer disease","volume":"91","author":"Strittmatter","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"18694","DOI":"10.1073\/pnas.0508254102","article-title":"Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity","volume":"102","author":"Chang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0165-5728(00)00459-8","article-title":"Apolipoprotein E modulates glial activation and the endogenous central nervous system inflammatory response","volume":"114","author":"Lynch","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/42257","article-title":"Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E","volume":"388","author":"Barger","year":"1997","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1385\/JMN:23:3:205","article-title":"A dual role for apolipoprotein e in neuroinflammation: Anti- and pro-inflammatory activity","volume":"23","author":"Guo","year":"2004","journal-title":"J. Mol. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101594","DOI":"10.1016\/j.smim.2022.101594","article-title":"APOE mediated neuroinflammation and neurodegeneration in Alzheimer\u2019s disease","volume":"59","author":"Parhizkar","year":"2022","journal-title":"Semin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000026195","article-title":"Apolipoprotein E polymorphism in elderly Chilean people with Alzheimer\u2019s disease","volume":"18","author":"Quiroga","year":"1999","journal-title":"Neuroepidemiology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1590\/S0100-879X2003000700013","article-title":"Association of apolipoprotein E polymorphism in late-onset Alzheimer\u2019s disease and vascular dementia in Brazilians","volume":"36","author":"Souza","year":"2003","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_51","first-page":"371","article-title":"Associations between apolipoprotein e gene polymorphisms and Alzheimer\u2019s disease risk in a large Chinese Han population","volume":"10","author":"Wu","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1038\/s41467-020-18198-x","article-title":"Association of APOE e2 genotype with Alzheimer\u2019s and non-Alzheimer\u2019s neurodegenerative pathologies","volume":"11","author":"Goldberg","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.1523\/JNEUROSCI.5302-08.2009","article-title":"Macrophage-mediated degradation of beta-amyloid via an apolipoprotein E isoform-dependent mechanism","volume":"29","author":"Zhao","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_54","unstructured":"Prince, M., Wimo, A., Guerchet, M., Ali, G.-C., Wu, Y.-T., and Prina, M. (2015). World Alzheimer Report 2015 The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends, Alzheimer\u2019s Disease International."},{"key":"ref_55","first-page":"313","article-title":"The Epidemiology of Alzheimer\u2019s Disease Modifiable Risk Factors and Prevention","volume":"8","author":"Zhang","year":"2021","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1212\/WNL.0000000000004897","article-title":"Dementia in Latin America: Assessing the present and envisioning the future","volume":"90","author":"Parra","year":"2018","journal-title":"Neurology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1590\/1516-4446-2019-0735","article-title":"Early diagnosis and treatment of Alzheimer\u2019s disease: New definitions and challenges","volume":"42","author":"Pais","year":"2020","journal-title":"Braz. J. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Das","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_59","first-page":"110","article-title":"A randomized controlled study to evaluate the effect of bexarotene on amyloid-\u03b2 and apolipoprotein E metabolism in healthy subjects","volume":"2","author":"Ghosal","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1750-1326-5-44","article-title":"Systemic treatment with liver X receptor agonists raises apolipoprotein E.; cholesterol, and amyloid-\u03b2 peptides in the cerebral spinal fluid of rats","volume":"5","author":"Suon","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.mcn.2007.01.011","article-title":"The LXR agonist TO901317 selectively lowers hippocampal Abeta42 and improves memory in the Tg2576 mouse model of Alzheimer\u2019s disease","volume":"34","author":"Riddell","year":"2007","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2174\/156720507780362227","article-title":"Role of LXR and ABCA1 in the Pathogenesis of Alzheimers Disease -Implications for a New Therapeutic Approach","volume":"4","author":"Koldamova","year":"2007","journal-title":"Curr. Alzheimer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13195-016-0173-2","article-title":"Double-blind, placebo-controlled, proof-of-concept trial of bexarotene Xin moderate Alzheimer\u2019s disease","volume":"8","author":"Cummings","year":"2016","journal-title":"Alzheimers Res. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1111\/jnc.12484","article-title":"Blocking the apolipoprotein E\/amyloid \u03b2 interaction in triple transgenic mice ameliorates Alzheimer\u2019s disease related amyloid \u03b2 and tau pathology","volume":"128","author":"Liu","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/S0002-9440(10)63355-X","article-title":"A synthetic peptide blocking the apolipoprotein E\/beta-amyloid binding mitigates beta-amyloid toxicity and fibril formation in vitro and reduces beta-amyloid plaques in transgenic mice","volume":"165","author":"Sadowski","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3233\/JAD-2011-101401","article-title":"Blocking the apolipoprotein E\/amyloid-\u03b2 interaction reduces fibrillar vascular amyloid deposition and cerebral microhemorrhages in TgSwDI mice","volume":"24","author":"Yang","year":"2011","journal-title":"J. Alzheimers Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.cbpa.2008.03.009","article-title":"Peptidomimetics, a synthetic tool of drug discovery","volume":"12","author":"Vagner","year":"2008","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"20406223221081604","DOI":"10.1177\/20406223221081605","article-title":"Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer\u2019s disease?","volume":"13","author":"Vecchio","year":"2022","journal-title":"Ther. Adv. Chronic. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"146685","DOI":"10.1016\/j.brainres.2020.146685","article-title":"ApoE mimetic improves pathology and memory in a model of Alzheimer\u2019s disease","volume":"1733","author":"Krishnamurthy","year":"2020","journal-title":"Brain Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.3233\/JAD-191185","article-title":"The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction","volume":"75","author":"VanDusen","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"7281","DOI":"10.1523\/JNEUROSCI.0646-14.2014","article-title":"Anti-ApoE antibody given after plaque onset decreases A\u03b2 accumulation and improves brain function in a mouse model of A\u03b2 amyloidosis","volume":"34","author":"Liao","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1084\/jem.20121274","article-title":"Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of A\u03b2 amyloidosis","volume":"209","author":"Kim","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/ana.26043","article-title":"Apolipoprotein E4 Reduction with Antisense Oligonucleotides Decreases Neurodegeneration in a Tauopathy Model","volume":"89","author":"Litvinchuk","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.neuron.2017.11.014","article-title":"Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of \u03b2-amyloidosis","volume":"96","author":"Huynh","year":"2017","journal-title":"Neuron"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41591-018-0004-z","article-title":"Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector","volume":"24","author":"Wang","year":"2018","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/0197-4580(95)00021-6","article-title":"Staging of Alzheimer\u2019s disease-related neurofibrillary changes","volume":"16","author":"Braak","year":"1995","journal-title":"Neurobiol. Aging"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/1941\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:39:00Z","timestamp":1760114340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/60\/12\/1941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":76,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["medicina60121941"],"URL":"https:\/\/doi.org\/10.3390\/medicina60121941","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]}}}