APP and dementia: Although the 50% increase in APP expression that would be predicted as a consequence of gene loading (1.5×) in trisomy, may not be sufficient to result in the characteristic pathophysiology of DS, but, together with its induction of IL-1 and the resultant increase in APP, may be responsible, at least in part, for the role of APP gene triplication as a determinant of the age at onset of dementia in DS [64] and in the development of the neuropathological changes of AD in DS [65].