Section 1 is a brief review of pertinent clinical, etiologic, and epidemiologic features of DS. This Section provides background information helpful in understanding the cellular and molecular interactions described in Section 2. Section 2 is a description of how leptin and adiponectin affect various signaling factors involved in the DS, Alzheimer’s disease, and cancer relationships, and how the underlying genetic consequences of trisomy 21 are involved in these relationships. This evidence concerns the gene LEP and early-onset autosomal dominant Alzheimer disease.