Changes in Alzheimer’s disease-related pathology were first investigated in parabiosis studies in which young transgenic mice carrying the human amyloid precursor protein (APP) gene containing Swedish mutations and the human presenilin (PS1) gene encoding the deleted exon 9 mutation (APPswe/PS1dE9) were joined with age-matched young wild-type animals90. This evidence concerns the gene PSEN1 and early-onset autosomal dominant Alzheimer disease.