Many factors involved in the neuropathology of AD in DS, including epigenetic factors, innate immunity and impaired haematopoiesis, contribute significantly towards the pathophysiology and the enhanced ageing processes seen in DS and as a consequence of the triplication of genes RUNX1, S100β and OLIG2, together with the influence of proteins that collectively protect from cellular defects and inflammation, which include hepcidin, ferritin, IL-6 and TREM2. The gene discussed is TREM2; the disease is Alzheimer disease.