{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ogg J"],"funding":["National Institute of Aging","NIA NIH HHS","Nancy and Buster Alvord Endowment"],"pagination":["24"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12411319"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["150(1)"],"pubmed_abstract":["Early onset familial Alzheimer's disease (EOFAD) is rare compared to sporadic AD, but dominant variants in genes involved in amyloid β (Aβ) processing are well-described. One such variant is in the presenilin 2 (PSEN2) gene, N141I, and was first described in a family with Volga German descent. Separately, individuals with Down syndrome (DS) are also at risk for early onset AD, having an extra copy of an amyloid precursor protein gene. While either can drive EOFAD alone, it is extremely rare for both to occur within one individual. Here we describe a unique case of a 48-year-old individual, with both DS and the PSEN2 N141I variant. We investigated whether having two high-risk AD variants results in worsened or distinct pathology compared to single variant carriers. Neuropathologic evaluatio"],"journal":["Acta neuropathologica"],"pubmed_title":["Down syndrome and a presenilin 2 variant: dual genetic risk of Alzheimer's disease."],"pmcid":["PMC12411319"],"funding_grant_id":["P30 AG066509"],"pubmed_authors":["Ogg J","Postupna N","Xiao M","Fonseca LM","Gibbons LE","Latimer CS","Ariza J","Jayadev S","Bird TD","Keene CD"],"additional_accession":[]},"is_claimable":false,"name":"Down syndrome and a presenilin 2 variant: dual genetic risk of Alzheimer's disease.","description":"Early onset familial Alzheimer's disease (EOFAD) is rare compared to sporadic AD, but dominant variants in genes involved in amyloid β (Aβ) processing are well-described. One such variant is in the presenilin 2 (PSEN2) gene, N141I, and was first described in a family with Volga German descent. Separately, individuals with Down syndrome (DS) are also at risk for early onset AD, having an extra copy of an amyloid precursor protein gene. While either can drive EOFAD alone, it is extremely rare for both to occur within one individual. Here we describe a unique case of a 48-year-old individual, with both DS and the PSEN2 N141I variant. We investigated whether having two high-risk AD variants results in worsened or distinct pathology compared to single variant carriers. Neuropathologic evaluatio","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-05-29T21:40:50.338Z","creation":"2026-04-08T06:05:21.058Z"},"accession":"S-EPMC12411319","cross_references":{"pubmed":["40906048"],"doi":["10.1007/s00401-025-02931-1"]}}