Studying Down syndrome might help us understand Alzheimer’s disease better
The second feature of Alzheimer’s disease is neurofibrillary tangles. These are made up of a protein called tau that builds up inside of neurons in the brain and prevents them from functioning properly.
For people without Down syndrome, these neurofibrillary tangles can start to develop anywhere from age 30 to over 100 years. But for people with Down syndrome these tangles do not start to accumulate until they are over 40 years old. This is another example of how it may be easier to understand Alzheimer’s disease in people with Down syndrome because we know the ages at which neurofibrillary tangles begin.
Other changes that are common in Alzheimer’s disease also happen with age in Down syndrome including increasing brain inflammation, oxidative damage and loss of proteins in synapses, which are the connections between nerve cells of the brain. All of these features may lead to impaired brain function.
When we learn more about when these changes happen, we can also start to think about ways to prevent or reverse them.
What does dementia look like in people with Down syndrome?
Many people are aware of the early warning signs of Alzheimer’s disease and that the loss of short-term memory is one of the key features.
For people with Down syndrome the evidence suggests similar changes may also happen in cognition and behavior as in the development of Alzheimer’s disease. Memory and thinking changes also appear in dementia with Down syndrome, but are more difficult to observe because of the nature of the intellectual disability.
But other changes, like social withdrawal, mood changes (including anxiety and depression), aggressive behavior, lack of interest in usual activities, change in sleep pattern and irritability, are easier to detect in Down syndrome. Similar changes also happen in people without Down syndrome who develop dementia in the moderate to severe stages of the disease.
What changes can we see in the brain by imaging?
The brains of people with Down syndrome have some differences compared to people of a similar age without Down syndrome. For example, in people in their 40s, the hippocampus of someone with Down syndrome may already show signs of atrophy (getting smaller) signaling early Alzheimer’s disease, a change we do not usually see in people without Down syndrome.
Our research group has been studying the connections between different brain structures by measuring white matter integrity – which is how well the long axons, the threadlike parts of neurons that connect to other neurons, are functioning. We do this by measuring how water molecules move along axons in people with Down syndrome.
We have found that the frontal lobes in people with Down syndrome may become increasingly disconnected from other parts of the brain. Similar changes in the white matter connections happen in Alzheimer’s disease in general.
In our study we see these changes in people in their late 30s, when we typically do not see these changes at all in people without Down syndrome.
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