Understanding what causes the increased risk of Alzheimer’s disease in Down’s syndrome

Read about a research project we funded on investigating cellular changes in Down syndrome that predispose to Alzheimer Disease.

Lead Investigator: Dr Frances Wiseman
Institution: University College London
Grant type: PhD studentship
Duration: 36 months 
Amount:  £91,000

Why did we fund this project?

Comments from members of our Research Network:

'This study has wider implications not just for those with Down's Syndrome.'

'This looks to be an exciting and potentially valuable PhD project. Pursuing the links between existing, known genetic disorders and brain related disorders in adults could produce insights for future research.'

'This is well thought through, which has the chance of eventually leading to a breakthrough in understanding the pathology of Alzheimer's disease.'

What do we already know?

People with Down's syndrome have an increased risk of developing Alzheimer's disease, usually at a relatively young age. Most people with Down's syndrome will have the Alzheimer's hallmark clumps of amyloid and tau proteins in their brain by the age of 40, and two thirds will have Alzheimer's by the age of 60.

Our genes are arranged on structures called chromosomes and a single chromosome contains several hundred different genes. Most people have 23 pairs of chromosomes but Down's syndrome is caused by having an extra copy of a particular chromosome, called chromosome 21. One of the known genetic links to younger onset dementia is the amyloid precursor protein (APP) gene, which is found on chromosome 21. This is thought to be the reason why people with Down's syndrome have an increased risk of Alzheimer's. 

However, the research team believes that there may be other genes present on this chromosome that also influence a person's risk of developing Alzheimer's disease. These genes are likely to have an effect on the amyloid precursor protein, causing it to form the toxic amyloid clumps associated with the condition. 

What does this project involve?

The PhD student will use cells in the lab that have an extra copy of chromosome 21 to understand the effects of the chromosome at the molecular level. The student will add amyloid precursor protein to these cells to understand how the extra chromosome affects this protein. The study will particularly focus on a component of the cell called endosomes, which are responsible for sorting and recycling toxic proteins within the cell. The researchers believe that the endosomes could be responsible for breaking down the amyloid precursor protein into the toxic fragments that cause damage to cells in Alzheimer's. The student will investigate how endosomes are affected by the extra chromosome. 

The student will use this information to understand which genes on chromosome 21 could be influencing the risk of Alzheimer's alongside the amyloid precursor protein.

How will this benefit people with dementia?

As people with Down's syndrome are known to be at increased risk of Alzheimer's disease, studying what causes this increased risk may shed light on the underlying causes of the disease. The researchers hope that identifying potential genes on chromosome 21 that can affect dementia risk will pave the way towards identifying new potential targets for treatment. This research could therefore be the first step in finding a way to prevent or treat dementia in people with or without Down's syndrome.