[en] With the increase in life expectancy, a higher prevalence of Alzheimer's disease is pre-dicted in our society. In recent years, many researches have been conducted to identify possible causes of this disease and to propose more specific treatments. Additionally, it is important to understand its etiopathogenesis in order to identify the actors involved in the predisposition to develop the disease, potentially allowing an early detection. In this work, in order to determine if there is a potentially causal relationship between DNA methylation in the placenta and the later onset of Alzheimer's disease in adult-hood, we conducted a Mendelian Randomization analysis using our own database of placental quantitative trait loci (mQTLs) and other publicly available datasets of adult and fetal brain tissue. We also conducted a search for summary statistics of Alzhei-mer's disease genome-wide association studies (GWAS) and formatted the obtained genomic data. Subsequently, Mendelian Randomization was performed using the SMR software and the results were characterized using online genomic search tools. Finally, the results were discussed and interpreted through a literature search. In summary, we found CpGs associated with Alzheimer's disease in the placenta near genes previously related to this disease, such as BIN1 and PICALM, but also others with relevant func-tions in fetal development, such as BCL3 and EPHA1-AS1. Thus, part of the genetic susceptibility to Alzheimer's disease may be expressed during prenatal stages through placental DNA methylation. The implicated CpG positions are located near genes relat-ed to neurodevelopment and appear to be specific to the placenta. However, further research will be necessary to corroborate our findings.

[eu] Bizi-itxaropenaren handitzearekin batera, gure gizartean Alzheimerraren prebalentziaren gorakada ere espero da. Azken urteotan, Alzheimer gaixotasuna etengabe ikertzen ari da gaixotasun honen kausak topatzeko asmotan, tratamendu zehatzagoak ezarri ahal izateko. Horrenbestez, garrantzitsua da haren etiopatogenia ezagutzea, Alzheimerraren garapenean parte hartzen duten faktoreak identifikatzeko, eta honenbestez, gaixotasuna garaiz detektatu ahal izateko. Ikerketa lan honetan, DNAaren metilazioa eta Alzheimerraren garapenaren arteko erlazioa ezagutzeko, ausaskotze mendeldar analisi bat egin genuen. Horretarako, lan honetan plazentaren DNAren metilazioaren eta helduaroan Alzheimerra garatzearen arteko erlazio kausala ikertu zen, horretarako plazentaren eta garun-ehun heldu eta fetalaren metilazioaren ezaugarri kuantitatiboen loci edo mQTLen datu-baseak erabilita. Horretaz gain, genoma osoko asoziazio-ikerketen edo GWASen laburpen-estatistikoak bilatu eta lortutako datu genomikoak formateatu ziren. Ondoren, Ausazkotze Mendeldarra burutu zen SMR softwarearen bidez eta lortutako informazioa hobeto ezagutzeko, bilatzaile genomikoetan ezaugarritu genuen. Bukatzeko, emaitzak eztabaidatu eta interpretatu genituen bilaketa bibliografiko bidez. Laburbilduz, hurrengo informazioa aurkitu genuen: Alzheimerrarekin asoziaturiko CpGak aurkitu genituen gaixotasun honekin aurretik erlazionaturiko genen ondoan (BIN1 eta PICALM), eta baita fetuaren garapenean paper bat duten geneen ondoan ere (BCL3 eta EPHA-AS1). Hori horrela, Alzheimerraren suszeptibilitate genetikoaren zati bat jaio aurretiko faseetan adieraz liteke plazentaren DNAren metilazioari esker. Parte hartzen duten CpG posizioak garapen neuronalarekin zerikusia duten genen ondoan daude, eta posizio hauek oso plazenta-espezifikoak direla ematen du. Hala eta guztiz ere, ikerketa gehiago behar izango da gure aurkikuntzak berresteko.