Longevity Briefs: A New Way To Slow Brain Ageing And Prevent Dementia

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

It seems that a group of cells called astrocytes play a pivotal role in maintaining brain health and preventing dementia. Astrocytes reside in the brain and play a maintenance and repair role, supporting the ability of neurons to function by providing them with nutrients, regulating blood flow and influencing the development of new synapses. With advancing age, however, astrocyte function appears to decline. In this study, researchers focus on one facet of this decline and investigate whether it might be targeted to improve brain function not just in disease, but also in healthily ageing people.

The discovery:

Researchers focussed on a molecule called Hevin that is released by astrocytes. Hevin promotes synapse formation, while a closely related molecule called SPARC does the opposite. Previous research suggested that SPARC production by astrocytes increases in Alzheimer’s disease while Hevin production decreases. To see if this could be addressed, the researchers took 11 month-old mice with genetically-induced Alzheimer’s disease and treated them with an adeno-associated virus (AAV) containing genetic material encoding the Hevin protein. While untreated mice had very low levels of Hevin, the treated mice not only produced more Hevin, but also performed significantly better in several cognitive tests 5-6 months post-treatment. For example, when tasked with finding the exit within a maze, treated mice learnt significantly faster than untreated mice.

The researchers then went one step further, repeating the experiment on 6-month old normal mice and performing cognitive tests after 1 month. Once again, the mice treated with Hevin AAVs performed significantly better than the untreated mice, though not in every test.

The implications:

So, it seems as though boosting Hevin production is enough to improve cognition, at least in mice, but how? Despite the observed improvements, there were no differences in the amount of amyloid beta (a protein thought to contribute to Alzheimer’s development) between treated and untreated mice. There were however significant differences in many proteins involved in synapse development and in particular those related to actin. Actin proteins arrange into long filaments that form an integral part of a cell’s structural skeleton, and also allow cells to change shape and to move, making it essential for synapse formation.

While the prospect of a molecule that can improve cognition in both health and disease is exciting, any human implications are likely to be a long way off. This study used BL/6 mice, an inbred strain of mice that develop many severe health problems that wild mice don’t have. This can make treatments look more promising than they really are, as they may simply be compensating for genetic defects that do not exist in real world, genetically diverse populations. Mouse models of Alzheimer’s disease are also generally quite poor models of human disease, since mice do not live long enough to get Alzheimer’s and so must be genetically modified to develop the disease at a rapid pace. New Hevin AAVs would also need to be developed for human use, since the AAVs used in this study were designed for use in mice.