INFLAMMATORY MECHANISMS IN ALZHEIMERS-DISEASE

In recent years many studies have indicated an involvement of inflamma tory mechanisms in Alzheimer's disease (AD). Acute-phase proteins such as alpha 1-antichymotrypsin and c-reactive protein, elements of the c omplement system, and activated microglial and astroglial cells are co nsistently found in brains of AD patients. Most importantly, also cyto kines such as interleukin-6 (IL-6) have been detected in the cortices of AD patients, indicating a local activation of components of the uns pecific inflammatory system. Up to now it has remained unclear whether inflammatory mechanisms represent a primary event or only an unspecif ic reaction to brain tissue damage. Therefore, we investigated whether IL-6 immunoreactivity could be found in plaques prior to the onset of neuritic changes, or whether the presence of this cytokine is restric ted to later stages of plaque pathology. We confirmed our previous obs ervation that IL-6 is detectable in a significant proportion of plaque s in the brains of demented patients. In AD patients IL-6 was found in diffuse plaques in a significant higher ratio as would have been expe cted from a random distribution of IL-6 among all plaque types. This o bservation suggests that IL-6 may precede neuritic changes, and that i mmunological mechanism may be involved both in the transformation from diffuse to neuritic plaques in AD and in the development of dementia.