Aim: The maturation of most T-lymphocyte precursors takes place within the meshwork of thymic epithelial cells. Different steps of this process can be defined by immunologic phenotyping. The prothymocytes are positive for the terminal deoxynucleotidyl transferase (TdT) and give rise to cortical thymocytes, which express CD1, CD2, CD3, CD5, and both CD4 and CD8. These CD4 and CD8 double-positive cortical thymocytes differentiate into two lineages: CD4+ or CD8+ lymphocytes of the thymic medulla, by the tenth week of gestation. Our study points towards the determination of the CD8 cytotoxic/suppressor capacity of the fetal thymus in Down's syndrome.
Experimental Design: A quantitative comparison of T-lymphocytes (CD3, CD4, and CD8) in the thymic parenchyme in embryos after voluntary abortion during 2nd trimester of gestation and embryos with Down's syndrome, respectively, was performed.
Results: Our results showed: 1) A statistically significant depletion in the total number of T-cells (CD3 positive) in the cases of embryos with Down's syndrome over those after voluntary abortion, during the second trimester of gestation (p<0.0001, t-test). 2) A significant difference in the CD8/CD4 ratio in the cases of embryos with Down's syndrome, during the second trimester of gestation which was numerically stronger with the progress of fetal development (20th week: p<0.025; 24th week: p<0.01, chi-square).
Conclusions: The occurrence of increased CD8/CD4 ratio in the cases with Down's syndrome, in the second trimester of gestation, underlines the cytotoxic/suppressor property of the thymus in the affected fetuses.
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Alzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.
Method: We compared scores on the Research Attitudes Questionnaire (RAQ) of individuals enrolled in two recruitment registries: the UCI Consent to Contact [C2C (N = 4818)] and DS-Connect (N = 976).
Alzheimers Dement
December 2024
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
Background: Increased APP gene dosage is both necessary and sufficient to result in Down Syndrome Alzheimer's Disease (DSAD) in humans and AD-related degenerative changes in mouse models of DS.
Method: We tested antisense oligonucleotides (ASOs) designed to suppress APP expression via RNAseH1-mediated degradation in the Dp(16)1Yey or Dp(16) model of Down Syndrome. Dp(16) is trisomic for human chromosome 21 syntenic regions on murine chromosome 16, containing 115 genes including APP.
Background: Clinical assessments utilized in trials to measure progression in sporadic Alzheimer's disease (SAD) such as the MMSE, ADAS-Cog, CDR-SB and ADCS-ADL are well established. Distinct assessments are utilized for Down Syndrome-related Alzheimer's disease (DSAD). Although these assessments are less well established, they probe comparable domains of cognition and function.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Kansas Medical Center, Kansas City, KS, USA.
Background: Evidence in adults without Down syndrome (DS) suggests that exercise during mid-life improves cognitive function and decreases risk of later life dementia. Studies supporting this relationship in adults with DS are limited. The purpose of this study was to examine changes in cognitive function after a 12-mo exercise intervention in adults with DS without dementia.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, São Paulo, Brazil.
Background: Sleep-related breathing disorders are commonly reported in the Down Syndrome (DS) population, but data on its prevalence and severity are scarce, especially for the adult population. The increase in life expectancy and premature aging in patients with DS reinforces the need for an assessment of sleep quality. This study evaluated sleep-disordered breathing in adults with DS using sleep measures by polysomnography.
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