Why do we develop Alzheimer's disease in old age?

"Neurodegenerative diseases" is a collective term for disorders in which nerve cells in the brain degenerate and die. This type of disease leads to a progressive loss of physical and cognitive abilities. Examples of neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease and multiple sclerosis (MS). Each of these diseases has its own characteristic symptoms and progression.

The most common neurodegenerative disease is Alzheimer's disease. It is also the most common cause of dementia, the progressive decline of various mental abilities. There are currently about 1.8 million people living with dementia in Germany, and the incidence is on the rise (Blotenberg et al., 2023). The increasing number of people with Alzheimer's disease is not only an enormous burden for patients and their families, but also a political, social and economic challenge. It is therefore particularly important to continue research into the disease in order to develop more effective treatments in the future. Ageing is the main risk factor for Alzheimer's disease - the older we get, the higher the risk of developing the disease. Typical symptoms of the disease include memory loss, orientation and speech disorders, agitation and behavioural changes.

Alzheimer's disease is characterised by the slowly progressive death of nerve cells and nerve cell contacts. Beta-amyloid and tau proteins are thought to be the cause of nerve cell death (Scheltens et al., 2016). Beta-amyloid proteins stick together and accumulate as 'plaques' between nerve cells. As the disease progresses, tau proteins also clump together and accumulate inside the nerve cell. These protein deposits lead to an inflammatory response from the surrounding immune cells, which in turn fuel the progression of the disease in various ways (Heneka et al., 2015). Microglia, the primary immune cells of the central nervous system (CNS), are important for maintaining brain health and function. However, microglia are also thought to be key players in the pathogenesis of Alzheimer's disease. It is not yet clear how exactly they are involved in the disease mechanism (Hansen et al., 2018).

How microglia change with age, how this affects neighbouring cells and how these changes may contribute to the development and progression of neurodegenerative diseases is being investigated at our institute by Hannah Scheiblich. The department of Anne Schaefer is also exploring the role of immune cells in neurodegenerative diseases and brain ageing, in particular the epigenetic mechanisms of microglial adaptation and microglia-mediated neuronal pathology.