APP and Alzheimer disease: Such observations of significantly more frequent CAA, and a greater severity of CAA when present, in people with DS relative to sLOAD and control cases are consistent with the hypothesis that such changes are driven, at least partially, by an overexpression of APP. The lack of AD neuropathology and CAA, even at greater than 70 years of age, in rare cases of DS with partial trisomy 21 where APP is not overexpressed [12, 35] would be consistent with this argument.