Abstract Background: Down syndrome (DS, Trisomy 21) is a genetic disease resulting from the presence of all or part of an extra 21 chromosome and may affect the function of any organ and system. It is the most common chromosomal ab-normality, with a frequency of 1:800 to 1:1000 births. In Egypt, it varies between 1 in 555 in one study to 1 in 770 in another. Amyloid Precursor Protein (APP) is a membrane protein concentrated in the synapses of neurons. APP prote-olysis generates beta amyloid (AR), which forms amyloid plaques found in the brains of Alzheimer's disease patients. In DS, there is increase in production of (AR), so children and adolescents are more susceptible for dementia and Alzhe-imer's disease. Aim of Study: It was to compare plasma Amyloid protein (AR) level in children suffering from DS with its level in the controls and correlation between (AR) level and Intelligent Quotient (IQ) of the studied subjects. Patients and MethoDS: This study was carried out on 40 Egyptian children divided into: 20 children with DS with age range (3-16 years) under follow-up at Genetics Unit of Pediatric Department Tanta University Hospital and 20 healthy children with normal karyotyping matched for sex and age. All patients and controls were subjected to complete history taking, clinical examination, and laboratory investigations including (karyo-typing, cholesterol & triglycerides level, thyroid function test, random blood sugar, Intelligent Quotient (IQ), and beta amyloid protein serum level. Results: Serum Beta amyloid protein level was signifi-cantly higher in children and adolescents with DS in compar-ison with healthy control. Conclusion: We concluded that serum Beta amyloid protein level was significantly higher in children and adoles-cents with DS in comparison with healthy control. We also concluded that there was a significant positive correlation between serum beta amyloid protein level and age of children and adolescents with Down syndrome and there is no corre-lation between AR and IQ.