Possible use of autologous stem cell therapies for Alzheimer's disease.

The statement, "neurodegenerative diseases are incurable because neurons do not regenerate during adulthood," has been challenged, and we have now found much evidence that the matured brain is capable of regenerating neurons. In our previous study, human neural stem cells (HNSCs) transplanted into aged rat brains differentiated into neural cells and significantly improved the cognitive functions of the animals, indicating that HNSCs may be a promising candidate for neuro-replacement therapy. However, because of ethical and practical issues associated with HNSCs, development of autologous stem cell strategies may be desired. We established new technologies to differentiate adult human mesenchymal stem cells into neural cells by modifying cell fate decisions. We also found a pyrimidine derivative that increases endogenous stem cell proliferation and neurogenesis after peripheral administrations of this compound. Although these results may promise a bright future for clinical applications of stem cell strategies in Alzheimer's disease (AD) therapy, we must acknowledge the complexity of AD. For example, abnormal metabolism of the amyloid-beta precursor protein (APP) may affect stem cell biology, while the prevalence of amyloid-beta peptide (Abeta) toxicity theory in AD pathology tends to limit our focus on the physiological functions of APP. We found that excess APP in the environment causes glial differentiation of stem cells. Even though the glial activation may be useful to eliminate Abeta deposits, neuronal differentiation of stem cells is needed for replacement of degenerating neurons in the AD brain. Thus, further investigation of the influence of AD pathology on stem cell biology is required.