Disease relevance of Down Syndrome

• BACKGROUND: There is evidence that some mothers of infants with Down's syndrome have abnormal metabolism of folate and methyl, as well as mutations in folate genes, which are features that are also seen in neural-tube defects (NTD) [1].
• Studies of children with heart defects and chromosomal anomalies have led to the discovery that loss of an elastin gene can cause supravalvar aortic stenosis and that a 2 Mb deletion from 22q11 is second only to Down's syndrome as a cause of heart defects [2].
• Is absence of atheroma in Down syndrome due to decreased homocysteine levels [3]?
• Deficiencies of interferon have also been noted in Down's syndrome, cellular immunodeficiencies, uremia, malnutrition, and hematopoietic malignancy [4].
• The amino acid composition, molecular mass, and NH2-terminal sequence of this amyloid protein are almost identical to those described for the amyloid deposited in the congophilic angiopathy of Alzheimer disease and Down syndrome, but the plaque core proteins have ragged NH2 termini [5].

Psychiatry related information on Down Syndrome

• Overexpression of the gene encoding the beta-amyloid precursor protein (APP) may have a key role in the pathogenesis of both Alzheimer's disease (AD) and Down Syndrome (DS) [6].
• Transferrin iron saturation was higher in the Alzheimer (58.9%) and Down syndrome groups (81.6%) than in the controls (39.0%) or stroke dementia patients (33.4%) [7].
• Taken together, our data show that overdosage of Sim2 may be important for the pathogenesis of Down's syndrome, especially mental retardation [8].
• These antibodies were found to immunostain tangles in normal aged brain and in brains affected by a range of neurodegenerative disorders, including Down's syndrome, Alzheimer's disease plus Parkinson's disease, progressive supranuclear palsy, and the parkinsonism-dementia complex of Guam, as well as Pick bodies in Pick's disease [9].
• RESULTS: The parents of the autistic probands had significantly higher rates of major depressive disorder and social phobia than the parents of the Down's syndrome probands [10].

High impact information on Down Syndrome

• Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome [11].
• This region contains the human homologue of a Drosophila gene, minibrain, and strongly implicates it in learning defects associated with Down syndrome [12].
• In screening for Down's syndrome in the second trimester of pregnancy, the concentrations of alpha-fetoprotein, the beta subunit of human chorionic gonadotropin, and intact human chorionic gonadotropin in material serum are widely used markers [13].
• Single-minded and Down syndrome [14]?
• Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease [15].

Chemical compound and disease context of Down Syndrome

• Measuring serum alpha-fetoprotein, chorionic gonadotropin, and estriol is more effective in screening for fetal Down's syndrome than measuring maternal serum alpha-fetoprotein alone [16].
• Thus glucose utilization by the brain appears to be excessive in young adults with Down's syndrome but may decline with age in some brain regions [17].
• Polyol profiles in Down syndrome. myo-Inositol, specifically, is elevated in the cerebrospinal fluid [18].
• Response of hematopoietic cell lines derived from patients with Down's syndrome and from normal individuals to mitomycin C and caffeine [19].
• No significant difference between Down syndrome and controls was found for CSF concentrations of mannitol, sorbitol, galactitol, ribitol, arabitol, or 1,5-anhydrosorbitol, but plasma mannitol, ribitol and arabitol were elevated in Down syndrome [18].

Biological context of Down Syndrome

• The rate of detection of Down's syndrome was 53 percent and the false positive rate was 5 percent when alpha-fetoprotein, the beta subunit of human chorionic gonadotropin, the maternal age were used together as predictors [13].
• To investigate the possible involvement of Cu/Zn-superoxide dismutase (CuZnSOD) gene dosage in the neuropathological symptoms of Down's syndrome, we analyzed the tongue muscle of transgenic mice that express elevated levels of human CuZnSOD [20].
• The cerebral metabolic rate for glucose, as measured with positron emission tomography and fluorine-18-labeled 2-deoxy-D-glucose, was significantly higher in four healthy young subjects with trisomy 21 syndrome (Down's syndrome) than the mean rate in healthy young controls [17].
• Genetic abnormalities (e.g. certain beta APP mutations or Down syndrome) and age-related changes in brain metabolism (e.g. reduced energy availability or increased oxidative stress) may favor accumulation of [Ca2+]i-destabilizing beta-amyloid peptide and diminish the release of [Ca2+]i-stabilizing, neuroprotective APPss [21].
• The p493F12 gene maps to the human chromosome 21q21 region, a region that may be important in the pathogenesis of AD and Down's syndrome [22].

Anatomical context of Down Syndrome

• Approximately 35 percent of all cases of Down's syndrome in fetuses can be detected by measuring maternal serum alpha-fetoprotein during the second trimester in the general population of pregnant women [16].
• Amyloid beta-protein is present in neuritic plaques and cerebrovascular deposits in individuals with Alzheimer's disease and Down's syndrome [23].
• From a genetic mosaic screen, we find that a lethal mutation in the Drosophila Down syndrome cell adhesion molecule (Dscam) specifically perturbs segregation of axonal branches in the mushroom bodies [24].
• Amniotic fluid AFP levels and Down syndrome [25].
• BACKGROUND & AIMS: Molecular misreading of the ubiquitin B gene has been documented in the cerebral cortex of patients with Alzheimer's disease and Down syndrome [26].

Gene context of Down Syndrome

• Immunocytochemical studies of brain tissue from 26 patients with Down's syndrome showed that the deposition of A4 protein amyloid began in these patients approximately 50 years earlier than it began in 127 normal aging subjects studied previously, although the rate of deposition was the same [15].
• Our results indicate that Ets2 has a role in skeletal development and implicate the overexpression of Ets2 in the genesis of some skeletal abnormalities that occur in Down's syndrome [27].
• The frequencies of the MTHFR 677C-->T and MTRR 66A-->G mutations were evaluated in DNA samples from 157 mothers of children with Down syndrome and 144 control mothers [28].
• Intrigued by a possible association between a Down's syndrome gene and solid tumors, we monitored SIM2 expression in solid tumors [29].
• Moreover, humans with life-long elevation of brain and peripheral Abeta (e.g., patients with presenilin mutations or Down syndrome) could have reduced immune responses to Abeta vaccination [30].

Analytical, diagnostic and therapeutic context of Down Syndrome

• Amniocentesis was offered when the risk of Down's syndrome, calculated as a function of maternal age and maternal serum alpha-fetoprotein concentration adjusted for maternal weight and race, was 1:270 or higher, the risk for a 35-year-old woman [31].
• Mouse trisomy 16 (Ts 16) is an animal model of Down syndrome [32].
• Cerebral cortical astroglia from the trisomy 16 mouse, a model for down syndrome, produce neuronal cholinergic deficits in cell culture [33].
• Immunocytochemistry performed with the anti-PTP monoclonal antibodies demonstrate PTP immunoreactivity within large pyramidal neurons--many of which contain neurofibrillary tangles in both AD and Down syndrome [34].
• Quantitative analysis of senile plaques in Alzheimer disease: observation of log-normal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome) [35].

References