Figure 2: Immune Signaling Is a Complex Multi-Dimensional Process in Neurodegenerative Disease.

Neurodegenerative diseases involve a complex interplay between immune signaling, genetics, and neural damage that result in debilitating cognitive phenotypes. The neuronal and synaptic dysfunction and loss (top) in neurodegenerative disease can be mediated directly by protein accumulation/aggregation (both intracellular and extracellular), by genetic polymorphisms that modulate neuronal function, or by immune cell signaling (red arrows). Immune signaling in neurodegenerative disease can occur, in response to aggregated toxic proteins, in response to neuronal damage, and/or as result of genetic polymorphisms altering immune cell function (blue arrows). Protein aggregation can in turn also be altered by neuronal dysfunction, altered immune function, and/or genetic polymorphisms (black arrows). All of these interconnected effects lead to the memory loss, cognitive decline, motor dysfunction, and death that are the clinical manifestations of these debilitating diseases. Arrow color is indicative of the component being modulated.