Down syndrome is the most frequent cause of cognitive dysfunction that results from the triplication of chromosome 21. Along with a number of developmental disabilities that occur in early childhood, Down syndrome is also associated with age-related Alzheimer’s disease neuropathology, leading to 50-70% of persons with Down syndrome showing dementia by 6th to 7th decade of life. Recent evidence has strongly implicated inflammatory processes in the pathogenesis of Alzheimer’s disease. However, little is known about the genetic impact of Down syndrome on neuroinflammation. Accordingly, the central aim of this chapter is to explicate our current knowledge of inflammation in Alzheimer’s disease and to discern how it may be extrapolated to understand better the inflammatory processes that affect Down syndrome neuropathology.