Chapter 18: Possible Clinical Applications of Stem-Cell Strategies in AD Therapies Check Access

Neural stem cells (NSCs) existing in the adult brain respond to pathological conditions suggesting the body's natural abilities of regeneration. Persistence of neurogenesis in Alzheimer's disease (AD) may promise a bright future for clinical applications of stem cell strategies in AD therapies. However, the endogenous NSC population is reduced by aging, stress, and disease. Thus, augmentation of the stem cell population may be effective for AD. Although embryonic stem (ES) cell or tissue-associated stem cell transplantation prove to be a valuable strategy for replenishing degenerating cells, a number of technical and ethical issues need to be addressed in developing effective clinical applications.

An alternative approach is use of induced pluripotent stem (iPS) cells, which are mitotically active, actively self-renewing, proliferating, and dividing at a rate equal to ES cells and capable of differentiation in a fashion similar to ES cells into fully differentiated tissues, including neurons. Another approach is to treat patients with therapeutic substances that augment endogenous NSCs. Many endogenous mitotic and growth factors have physiological roles in proliferation of NSCs, but their utility as a pharmacological agent is restricted due to their broad activity spectrum and limited permeability across the blood-brain barrier (BBB). A more effective and practical strategy would be to identify small molecular compounds that can cross the BBB and, in particular, stimulate the proliferation of NSCs. In this chapter, we will discuss the possibility of these cell based and pharmaceutical approaches for AD therapy with consideration of effect of AD pathological environments on NSC biology.