الفهرس 
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Abstract
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own syndrome (DS), the most common genetically based mental retardation disorder, is caused by the presence of an extra copy of chromosome 21 (trisomy 21). DS is characterized by a variety of deficits that affect many systems including skeletal, skin, immune and nervous. Although a high degree of variability among individuals has been described, the nervous system dysfunctions include severe impairments in learning, memory, speech and motor behavior.
Chromosomal triplication in DS invariably includes the APP gene (21q21) that encodes the amyloid precursor protein, APP. Endoproteolytic cleavage of APP yields the pathogenic amyloid-β peptides (Aβ) that progressively accumulate in the brain as the diffuse and neuritic plaques of Alzheimer’s disease (AD). In DS, cerebral Aβ accumulation is greatly accelerated and leads to invariant early-onset AD neuropathology and age-dependent neurocognitive sequelae. Concurrently, the Nerve Growth Factors (NGF), which acts on certain neurons of the central nervous system and the peripheral nervous system, helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses, has been suggested that it might be useful in reversing cholinergic
D
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neurodegeneration in DS. In the brain, NGF is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. NGF itself is important for long-term memory. Accordingly, the aim of the present study was to find the relationship between NGF and APP in patients with DS and their impact on neuropsychological evaluation.
Forty Down syndrome children participated in our study compared to forty matched healthy normal children. There was no significant difference in mean ± SD of age and weight in Down syndrome patients compared to controls. While the mean ±SD of height was shown to be significantly lower among Down syndrome patients. Mental retardation and short stature are among the features of Down syndrome phenotype, which are attributed to neuromuscular disorder caused by chromosomal imbalance.
In the present study APP was significantly higher in serum of Down syndrome cases compared to controls. This study is consistent with previous studies, 1.5-fold increased levels of APP among elderly DS patients compared to controls. Providing further evidence, soluble and insoluble Aβ increase as a function of age in DS frontal cortex. Ts65Dn mice (transgenic model for DS patient)
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shows increased over expression of APP, which increases by aging .
Results of the present study show that NFG in blood was significantly higher among DS patients compared to controls. NFG is a target-derived neurotrophic factor that acts through its specific receptors to enhance the survival, differentiation, and maintenance of specific neurons of the peripheral and central nervous systems. This result agrees with previous results of, who found that plasma levels of NGF were higher in children, adult and old DS subjects at age cohorts of demented DS subjects of three different age-cohorts (2-14 years; 20-50 yrs; >60 yrs) compared to controls, but also a significant age-related decrease of NGF levels was present in DS subjects . It is believed that the increase in NGF level in blood of DS patients act as a protective mechanism to reverse neural degeneration .
Present results shows that mean and SD of Wechsler was highly significant lower among Down syndrome patients compared to controls.It is well documented that the IQ in DS is usually in the moderately to severely retarded range (Gibson, 1978). DS is associated with various neurological complications, including cognitive deficits, seizures, early-onset dementia and motor dysfunction .
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Most recently, it was showed that children with DS followed the same motor development sequence and generally take twice the time for reaching gross motor developmental milestones attain motor skills compared to healthy equals. reported that motor deficits in children who weighed <1,250 g at birth without severe disabilities correlated with cognitive impairment, especially in the visuomotor domain revealed that late walkers had a significantly lower cognition and social adaptive function scores than early walkers among children with a history of preterm birth, but without major neurodevelopmental impairments. However, in children with DS, there was no significant correlation between early motor development and later cognitive function. These study results are consistent with results of the present study. However, it is not consistent with previous results, who reported that children with DS 6–10 years old achieved better scores in nonverbal tests, including visuomotor processing than verbal tests when they used the Differential Scales of Intellectual Efficiency.
Results in the present study showed a significant positive correlation between NFG and APP in the serum of DS patients and among controls. This indicates that neural regeneration in DS is an ongoing process, but it is not able to counterbalance by the degenerative damage.Increased levels of APP also markedly decreases retrograde transport of NGF
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and causes degeneration of forebrain cholinergic neurons in a mouse model of DS. It has been shown that APP deficiency results in a significant decrease in cell surface levels of the two NGF receptors, TrkA and p75NTR. Because APP has been shown to mediate intracellular trafficking of certain proteins one possibility is that APP can also regulate intracellular trafficking of TrkA and p75NTR through its interaction with these receptors. Therefore, an increase in the APP level could result in more TrkA/p75NTR at the cell surface and thus inhibit NGF endocytosis, whereas a decrease in the APP level could facilitate endocytosis of NGF upon its binding to TrkA and p75NTR.In vitro studiesusing PC12 cells or primary neurons have reported that NGF increases APP mRNA and protein levels .
Results in the present study show that that there has been a significant positive correlation between age and Wecsler among Down Syndrome patients which was non-significant among controls. It is well established that older age DS show significantly impaired performance on memory tests in comparison to the younger age DS. It is concluded that the more subtle cognitive impairments which associate to Alzheimer’s disease can be identified in the presence of a global cognitive impairment with sufficiently sensitive tests. In an increasing number of psychological studies there is evidence that adults with Down’s syndrome do acquire
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neuropsychological deficits). More tangential evidence for the development of Alzheimer’s disease in adults with Down ’syndrome, comes from studies employing positron emission and computer assisted tomography and electroencephalogram and MOO evoked potential latency recordings . The non-significant negative correlation between Amyloid Precursor Protein ng/ml and Wecsler among DS patients which was non-significant positive correlation between Amyloid Precursor Protein ng/ml and Wescler among controls indicates that APP plays a crucial in the impaired cognitive function associated with DS patients.
The significant positive correlation between age and NGF among DS patients, which was a non-significant positive correlation between age and NGF among controls, indicates that NFGif constantly secreted to repair the damage, which is so huge to be counteracted. showed that the number of neurons generated from trisomy 21 human Neural Progenitor Cells (hNPC) lines decreases dramatically with increased time in culture while age-matched euploidhNPCs continue to generate 20–30% neurons. Therefore, trisomy 21 hNPCs exhibit a developmentally regulated defect in neurogenesis that can be delineated in culture. Another study showed a reduction in proliferative capacity of the adult NSC population of the hippocampus in both young and old adult Ts65Dn mice . These previous studies in provide an evidence
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for impairment in neurogenesis and regenerative capacity of neural progenitor cells , which implies that NGF secreted in the brain is incapable of repair of damaged neurons due to their early ageing.
Conclusion:
In conclusion a significant increase in serum level of NGF indicates that regeneration is an ongoing process in DS patients. However, this regeneration cannot counterbalance the damage induced by APP increased dosage