Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes.
The combined MTHFR 677TT/MTR 2756AA genotype was associated with increased DS risk (P=0.034), and the combined MTHFR 1298AC/TYMS 2R/2R genotype with reduced risk (P=0.003).
This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (MTHFR 677C>T and 1298A>C, MTRR 66A>G, MTR 2756A>G, RFC1 80G>A and TYMS 28bp repeats and 1494 6bp deletion).
There is an increased risk of myeloid malignancy in individuals with Down's syndrome (DS), which is associated with a mutation in exon 2 of the transcription factor GATA-1.
This may be the case during pathological evolution of AD and DS when beta/A4 derived from synaptic APP is converted to beta/A4 amyloid by radical generation.
It is postulated that S-100 b protein may inhibit the development of neuroblastomas in Down's syndrome either antenatally, or after birth and may be a therapeutic agent against neuroblastoma.
In conclusion, the presence of three or more polymorphic alleles for MTHFR C677T, MTHFR A1298C, MTR A2756G, and RFC1A80G, and plasma Hcy concentrations higher than 4.99 micromol/L are maternal risk factors for DS.
These observations suggest that the development of pathological changes in DS brains does not parallel that observed in AD, which might be attributable to different causes in the pathogenesis of betaA4 formation.
This suggests that the decreased expression of PRDX2 may contribute to the altered redox state in DS at levels comparable to that of the increased expression of SOD1.
Patients were evaluated for risk of Down's syndrome and trisomy 18 based on biochemistry (free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A), nuchal translucency and the combination of both.
Aberrant protein expression of transcription factors BACH1 and ERG, both encoded on chromosome 21, in brains of patients with Down syndrome and Alzheimer's disease.
We hypothesize that overexpression of three genes, dap160/itsn1, synj/synj1, and nla/dscr1, located on human chromosome 21 play important roles in DS neurons.
These results indicate that the Down syndrome phenotype of this patient is due to microduplication of a chromosome 21 fragment containing the CuZn SOD gene.
These data suggest a role for ERG as a regulator of hematopoietic lineage potential, and that trisomy of ERG in the context of DS foetal liver hemopoiesis drives the pre-leukemic changes that predispose to subsequent DS-TMD and DS-AMKL.
Early pregnancy screening with the combined measurement of maternal serum PAPP-A and free beta-hCG and fetal nuchal translucency could achieve a high Down syndrome detection rate.
The methionine-synthase-reductase A66G, the methionine-synthaseA2756G and the cystathionine-beta-synthase 844ins68 polymorphisms were not associated with increased risk of Down syndrome.
In clinically relevant AML cell line models, high cystathionine-beta-synthase transcripts in DS CMK cells were accompanied by 10-fold greater ara-C sensitivity and 2.4-fold higher levels of ara-CTP compared with non-DS CMS cells.