Insights into the progression of genetic Alzheimer's disease from tau PET

People with autosomal-dominant Alzheimer's disease have mutations in either APP, PSEN1, or PSEN2, and individuals with Down syndrome have an extra copy of the APP gene. In people with Down syndrome, however, elevated tau PET was measured in the entorhinal cortex before notable amyloid PET concentrations were observed, and earlier accumulation of tau after amyloid deposition was generally observed, compared with autosomal-dominant Alzheimer's disease. [...]despite slower amyloid deposition in people with Down syndrome, accumulation of tau was more rapid than in individuals with autosomal-dominant Alzheimer's disease. For people with mutations in the PSEN1 gene, which is most common in autosomal-dominant Alzheimer's disease, a difference in position of the mutation (ie, before or after residue 200 on the PSEN1 gene) might affect amyloid load and onset of clinical symptoms,8 and could account for some of the observed differences compared with people with Down syndrome, in whom the high amyloid load might be related to the extra copy of the APP gene.