Alzheimer’s disease and T21

Why Down syndrome?

Life expectancy in the population of persons with Down syndrome (DS) has increased dramatically in recent years and is now over 60 years in developed countries. Accordingly, it has also increased the interest in those complications that occur in adulthood and senescence.

Amongst the later, Alzheimer’s disease (AD) is especially important. By the age of 40, all subjects present AD pathological changes in the brain. Although not all individuals with DS will develop dementia. The prevalence of AD increases with age, from 20-50% when aged 54 to 59 years, to 60-75% when older than 60 years. 

The main reason for this high risk is related to an increased accumulation of  the amyloid beta (Aβ) peptide in the brain as Trisomy 21 in DS involves, among others, the over-expression of the amyloid precursor protein (APP). Indeed, the chromosome 21 carries the APP gene.  


This ultra-high risk and universal pathological changes in adults with DS has led the scientific community to conceptualise DS as a form of genetically determined AD.

However, there is a gap in knowledge about the factors influencing the emergence of AD in DS given the variability in the age of presentation. Other factors (genetic or environmental) may play an important role in the development of AD.