Alzheimer’s disease is a major global health problem, with the number of people with the disease in the UK expected to double by 2050. Efforts to develop an effective treatment have not yet been successful as we don’t properly understand what causes it.
What do we already know about Alzheimer’s?
One of the key features of Alzheimer’s is the accumulation and spread of a protein called amyloid-beta, which aggregates to form ‘plaques’ inside the brain, and is thought to be a trigger for other disease-contributing changes. Although amyloid-beta is important, it doesn’t act alone. Inflammation, the process that occurs as part of the body’s immune response to infection, can occur in the brain through activation of immune cells called microglia, and it’s thought that this is one other factor that is part of the disease process.
How might inflammation be important?
A recent study by a group of researchers at the German Centre for Neurodegenerative Diseases and the University of Bonn looked to see whether inflammation has an effect on the increase and spread of amyloid-beta in the brain. They look specifically at something called the “inflammosome” in the microglial cells which is important for detecting signals of infection. In particular they look at a protein called ASC which is essential for allowing these signals to be acted on, but also aggregates together to form ‘ASC specks’ which can be released from the cells.
To investigate these ‘ASC specks’, the researchers use an animal model, a mouse type which is genetically engineered to produce a high level of amyloid beta and thus develop some symptoms which parallel the human disease. They also look in the brains of patients who died with Alzheimer’s disease, and compare them to brains of patients of the same age without the disease.
What does the new study show?
What they found is that the microglial cells produce more of the ‘ASC specks’, both in the brains of the Alzheimer’s patients and in the mouse model. Using cells from the mice, they also carry out further experiments which show that having more ‘ASC specks’ causes more amyloid-beta to aggregate.
Alzheimer’s is strongly dependent on age, but the researchers also show that even in young mice ‘ASC specks’ are present in the amyloid aggregates, with the same seen in patients with very early stage symptoms, indicating that this is an early event in the disease progression. Removing the gene needed to make the ASC protein from the mice, or using an antibody which blocks the protein both reduce the increase in amyloid-beta plaques, indicating that it could be a useful target to at least slow the disease.
Journal reference: Venegas, Carmen, et al. “Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease.” Nature 552.7685 (2017): 355. Available at: www.nature.com/articles/nature25158