Grant: Operating Grant

Alzheimer's disease (AD) is the most frequent cause of dementia in the ever increasing elderly population. AD causes a great deal of suffering to the patients, their families and caregivers. AD was considered for a long time a disease of the brain only, but it is now well recognised that, fundamentally, it also affects the rest of the body. It is widely suspected that a protein fragment (amyloid beta peptide, Ab) which accumulates in the brain in AD could be partly responsible. The accumulation of Ab also causes inflammation. Inflammation is a beneficial process when it is aimed at eradicating aggressors like the Ab, but if it becomes chronic, it can then harm individual organs as well as the whole body. The inflammatory process is mediated by our defence, or innate immune system. Following this first reaction , cells of the adaptive immune system - T lymphocytes - become sensitized to Ab and try to eliminate it by various strategies including helping specific autoantibody production by B cells. Interestingly, despite their apparent link to AD, Ab-reactive cells are also found in healthy people. Aging by itself alters our immune system for several reasons including infection with a common persistent virus (Cytomegalovirus), resulting in a less vigorous immune system, state termed: immunosenescence. We propose that with advancing age, the immune system becomes less effective in clearing Ab. Through its continuing but failing attempts to get rid of Ab, the immune system tires which then has deleterious side effects. Moreover, tiring of the immune system is accelerated by CMV infection, so we propose that CMV and AD could be linked. The objective of this project is to investigate immune status in patients with AD compared to patients with mild cognitive impairment and healthy elderly controls, in relation to CMV infection. This could lead to novel treatment strategies targeting inflammation and CMV infection.