PUB - Publikationen an der Universität Bielefeld

Alzheimer's disease (AD) is a devasting neurodegenerative disease afflicting mainly glutamatergic neurons together with a massive neuroinflammation mediated by the transcription factor NF-kappa B. A 65%-plus increase in Alzheimer's patients by 2050 might be a major threat to society. Hallmarks of AD are neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau and amyloid beta (A beta) plaques. Here, we review the potential involvement of transcription factor NF-kappa B by hereditary mutations of the tumor necrosis factor pathway in AD patients. One of the greatest genetic risk factors is APOE4. Recently, it was shown that the APOE4 allele functions as a null allele in human astrocytes not repressing NF-kappa B anymore. Moreover, NF-kappa B seems to be involved in the repair of DNA double-strand breaks during healthy learning and memory, a function blunted in AD. NF-kappa B could be a friend to healthy neurons by repressing apoptosis and necroptosis. But a loss of neuronal NF-kappa B and activation of glial NF-kappa B in AD makes it a foe of neuronal survival. Hopeful therapies include TNFR2 receptor bodies relieving the activation of glial NF-kappa B by TNF alpha.