Neurodegeneration and plasticity

AbstractNeurofibrillary degeneration, associated with the formation of paired helical filaments (PHF), is one of the critical neuropathological hallmarks of Alzheimer's disease (AD). Although the microtubule‐associated protein tau in a hyperphosphorylated form has been established as primary PHF constituent, the process of tau phosphorylation and its potential link to degeneration is not very well understood, mostly because of the lack of a physiological in vivo model of PHF‐like tau phosphorylation. PHF formation in AD follows a hierarchial pattern of development throughout different cortical areas, which closely matches the pattern of neuronal plasticity in the adult brain. Those brain areas are most early and most severely affected which are involved in the regulation of memory, learning, perception, self‐awareness, consciousness, and higher brain functions that require a life‐long re‐fitting of connectivity, a process based on a particularly high degree of plasticity. Failures of synaptic plasticity are, thus, assumed to represent early events in the course of AD that eventually lead to alteration of tau phosphorylation. Recently, we have used the hibernation cycle, a physiolog