Case report: A 50 year-old Down syndrome man exhibiting noAlzheimer’s disease biomarker profile nor cognitiveimpairment. Experience from the Argentine Initiative for theStudy of Down syndrome and Alzheimer’s

Abstract

Background: Down Syndrome (DS) is the most common genetic form of intellectualdisability. In recent years, there has been a significant increase in the life expectancyof individuals with DS, currently reaching the age of 60 or over. However, ithas been observed that as of age 40, these individuals experience higher risk ofdeveloping dementia, and almost all of them exhibit histopathological characteristicsof Alzheimer’s disease (AD) in their brains.As part of the first Latin American initiative for the study of Alzheimer’s disease inadults with Down syndrome (IASDA), we recruited a 50-year-old participant identifiedas SD8, who did not exhibit beta-amyloid brain deposition and showed no signs ofcognitive impairment.Method: The absence of beta-amyloid brain deposition was determined bypositron-emission tomography (PET) using an amyloid-binding compound (PiB) andquantification of cerebrospinal fluid biomarkers. To explore the possibility that lack ofAβ deposition could be due to an interstitial deletion of the APP gene, we performedArray-CGH and MLPA assays. Additionally, an exome analysis was conducted toassess the presence of Alzheimer’s protective gene variants. Induced pluripotentstem cells (iPSCs) were generated from SD8 peripheral blood mononuclear cells andsubsequently differentiated into neurons. This approach will enable a more in-depthstudy to gain further insights into this case.Result: These investigations revealed that SD8 possessed three copies of the APPgene, thus eliminating the possibility of an interstitial deletion. However, the exomeanalysis yielded no significant findings. Conclusion: In summary, in this study we present the strategies employed to delve intothe possible mechanisms of SD8 being an AD “escapee” and outline our planned stepsfor further investigation.