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This review examines genetic factors involved in the development of Alzheimer's disease (AD) in people with DS. A systematic search in major databases was conducted, and articles from 2020 to 2025 that met the predefined inclusion criteria were included. The results showed that the prevalence of AD was above 60% in people with DS older than 65\u2009years, the mean age at diagnosis was 53\u2009years, and the mortality occurred around 59\u2009years. The main genetic factor identified was the overexpression of the APP gene, along with other genes such as DYRK1A, RCAN1, SOD1, APOE\u03b54, and genes involved in the immune response, as well as posttranscriptional dysregulation. Diagnosis remains a challenge due to the pre\u2010existent intellectual disability and the atypical clinical presentation of the disease; however, the development of adapted neuropsychological tests, biomarkers, and neuroimaging techniques is expected to facilitate early diagnosis. 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