Neurodegenerative Diseases and the Aging Brain

The single biggest risk factor for neurodegeneration is advancing age. In this chapter, we focus on the changes that occur in the healthy aging brain and how these changes help to create an environment that is susceptible to different forms of neurodegeneration. In particular, we discuss the general declines in homeostatic quality controls in the aging brain—defects in protein quality control, mitochondrial dysfunction, increases in oxidative damage, and a general decline in the efficacy of DNA damage repair. Each of these declines places increasing stress upon the neuron and reduces its capability to respond to additional stressors. When combined with neurodegenerative stimuli, such as amyloid beta, tau, or alpha-synuclein deposits, the cell can enter into a vicious cycle of worsening performance and eventual cell death that underlies neurodegeneration and is distinct from the normal cognitive decline seen in older individuals.