image: Infographic: Sugar coating may play a role in resilience to Alzheimer’s disease
Credit: Netherlands Institute for Neuroscience
Some individuals are resilient to Alzheimer’s disease: they show the disease features of an ‘Alzheimer’s brain’ but do not exhibit clinical symptoms. What makes these individuals resilient? Researchers at the Netherlands Institute for Neuroscience have shown that one of the answers may lie in the groups of sugars and proteins enwrapping nerve cells in the brain, also known as the perineuronal nets. This discovery provides novel insight into how some people may escape cognitive decline despite Alzheimer’s disease changes in the brain.
Earlier research from the Netherlands Institute for Neuroscience has shown that it is possible for individuals to be resilient to Alzheimer’s Disease . These individuals show symptoms of the disease in their brain but do not show any memory deficits. Genetics and lifestyle play an important role in this resilience.
Building resilience
Cognitively challenging activities, such as sudoku or practicing multiple languages, as well as staying socially active can help build resilience against Alzheimer’s Disease. These activities would support the maintenance of the connections between nerve cells and stimulate them to be more flexible, As a result, nerve cells can easily increase their network and compensate for damaged or lost connections.
Brain plasticity, or the ability to form new connections between nerve cells, is obvious in children, as they are capable of learning much faster than adults. As the brain becomes older, the contact points between nerve cells become less flexible, because they are wrapped in a meshwork of proteins and sugars called perineuronal nets. These nets exert tight control over the brain’s plasticity, especially through their sugars, which limits our ability to form new memories. However, engaging in stimulating activities can reduce perineuronal nets.
Different perineuronal nets
Luuk de Vries and Daniela Carulli from the Laboratory for Neuroregeneration hypothesised that the brains of individuals resilient to Alzheimer’s would contain perineuronal nets that are different from those with Alzheimer’s disease. This is indeed what they found. While both contained lower levels of some proteins in the net, only resilient individuals showed a decrease in the net’s sugars. Additionally, while Alzheimer’s patients lost some of their synapses, the resilient subjects did not.
Luuk de Vries, first author of this study, says: “These findings show that there are differences between resilient donors and donors with Alzheimer’s, which have never been shown before. One hypothesis is that the sugars of the perineuronal net might be hindering the nerve cell’s ability to change and adapt. We saw less sugars in the nets of resilient brains, which might allow for higher plasticity. But we still don’t know what causes these changes”.
Protective properties
Aside from the finding above, another important discovery was the relation between perineuronal nets and the build-up of pTau, a toxic protein commonly found in Alzheimer’s Disease. Luuk de Vries: “Nerve cells surrounded by perineuronal nets do not show accumulation of pTau. It is possible that perineuronal nets protect nerve cells against the build-up of this protein. The Alzheimer’s brain also shows a higher expression of genes involved in the breakdown of proteins in the nets, meaning that nerve cells may be less protected from the toxic effects of pTau”.
Luuk de Vries concludes: “We believe that the resilient patients are better at coping with the loss of synapses caused by Alzheimer’s and somehow compensate for it. Changes in perineuronal nets might help these processes, but this is still a hypothesis. Our next step is to investigate this further, for instance in animal models .”
Source: Alzheimer’s & Dementia
Contact the researchers
Luuk de Vries: l.de.vries@nin.knaw.nl
Daniela Carulli: d.carulli@nin.knaw.nl