SOLUBLE CD40 LIGAND IN DEMENTIA

Some 15-20% of the population over the age of 65 years suffer from dementia, currently one of the leading causes of death behind cardiovascular diseases, cancer and cerebrovascular diseases. The major forms of dementia share in common overactivation of the CD40-CD40-L complex, leading to high levels of proinflammatory cytokine production by immune cells of the central nervous system (CNS), including microglia and astrocytes. Consequently, both neuronal survival and signaling are negatively affected, leading to the characteristic progressive loss of higher cortical functions. We have reviewed the literature concerning the involvement of this complex in the pathology of three major forms of dementia: Alzheimer's-type, HIV-associated and vascular dementia. This is followed by a discussion of current preclinical and clinical therapies that may influence this interaction, and thus point the way toward a future neuroimmunological approach to inhibiting the effects of CD40-CD40-L in neuropsychiatric disease.