Regulation of Immune Activity in Alzheimer’s Disease

Associate Professor Asya Rolls

Alzheimer’s disease (AD) is a neurodegenerative disorder that slowly impairs memory, cognition and eventually, the ability to perform even the simplest tasks. The tight link between aging and AD suggests that processes occurring during aging promote AD initiation and progression. Thus, understanding the transition from normal aging to AD pathology is crucial for early detection, prevention, and treatment of the disease. In recent years, strategies focused on modulation of immune activity, yielded promising results for AD treatment. These strategies are based on the idea that the immune system is the body’s major protection mechanism. However, with age, activity of the immune system declines and can further contribute to AD initiation and progression. Modulation of immune activity is an especially promising strategy for a complex disease such as AD, since there is no single factor (e.g. tau proteins, amyloid beta plaques or metabolic imbalances) that mediates the disease. Thus, boosting the endogenous mechanism that can restore tissue homeostasis, meaning the immune system, is a particularly promising strategy. However, immune system activity can be a double-edged sword, as imbalanced immune activation can exacerbate AD progression. Moreover, we still do not understand what goes wrong in the immune system that prevents it from protecting AD development in the aging brain, and in some cases, to even further exacerbate AD. Our preliminary data suggests a link between a decline in brain cholinergic activity and altered immunity, however, we do not understand how these changes impact AD. Thus, our long term goal is to understand how the decline in cholinergic activity, which characterizes the aging process, affects the involvement of the immune system in the course of AD pathology. We expect that such understanding will lead to the identification of early detection markers that can be potentially detected in the blood and uncover new targets within the immune system that upon modulation can prevent AD initiation and progression

Modulation of immune activity is an especially promising strategy for a complex disease such as AD, since there is no single factor (e.g. tau proteins, amyloid beta plaques or metabolic imbalances) that mediates the disease. Our goal is to understand how the decline in cholinergic activity, which characterizes the AD pathology, affects the involvement of the immune system in the disease.Asya Rolls