Increased APOE abundance in the brain in Down syndrome - Alzheimer’s disease compared with early onset-Alzheimer's disease is associated with elevated APP and its processing products

Trisomy of chromosome 21, the cause of Down syndrome (DS), is the most commonly occurring genetic cause of Alzheimer’s disease (AD). Here we compare the proteome of the frontal cortex of people who have Down syndrome-Alzheimer’s disease (DSAD) with demographically matched cases of early-onset AD and healthy ageing controls from the general population. We find the abundance of several chromosome 21 encoded proteins are increased in DSAD compared to both comparative groups. Moreover, wider dysregulation of the proteome occurs beyond proteins encoded by chromosome 21, including an increase in the abundance of the key AD protein APOE, in people with DSAD compared to matched cases of early-onset AD.