nonbeneficial functions: The significance of cellular change to cognitive function evolves in a hierarchy from the cell, to cellular units, to systems.
Each participating brain region in an overall system is selectively vulnerable to select genetic and/or environmental/disease-related conditions.
Dysfunction in one part of the system can compromise the entire connectionist network.
Dyshomeostasis is encoded into the network and alters input/output profiles, which may be optimal for the residual system, but the system now operates at another state function. Systems homeostasis/plasticity is understudied in aging, and that which is represented is largely limited to rodents.
Progressively more network plasticity and more good cells are required to maintain even normal baseline functions. This further weakens the linkages. One process affects the others.
Acute injury initiates inflammatory mechanisms. Inflammatory mechanisms include the activation of complement pathways that lead to cell lysis and the up-regulation of death receptors and their respective ligands. These death receptors in the immune system serve to maintain homeostasis through selective cell death by way of apoptosis. In the brain, acute inflammatory responses are part of the natural repair process, but chronic inflammation probably drives degeneration, much like a chronic infection. Thus, inflammatory mechanisms are another example of the delicate balance. Clearly, inflammatory mechanisms suppress the initiation phase as anti-inflammatory medications delay the age of onset for Alzheimer's disease. It is, of course, unknown at the present time whether the same interventions will be effective during the propagation phase, but there are strong arguments to indicate they will probably be ineffective. Inflammation and beneficial actions have also been dramatically brought to the forefront by the discovery that antibodies developed against amyloid can activate the immune system to cause the remove of senile plaques (Schenk et al., 1999). Thus the balance of immune activity in the nervous system is highly critical.
Some age-related risk factors such as Aβ, oxidative damage, and imbalances in glutamate may contribute to the emergence of inflammation and place cells at further risk for degeneration. Recent evidence suggests that reactive oxygen intermediates (ROIs) are potent inducers of FasL and that antioxidants suppress this transcriptional dependent process. Inhibition of FasL expression appears associated with decreased binding of nuclear factor NF-kB, an important redox-controlled transcription factor (Bauer et al., 1998). In response to oxidative stress, there is an increase in FasL expression