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Stem Cell Transplantation Strategies for the Restoration of Cognitive Dysfunction Caused by Cranial Radiotherapy

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Published on: October 18, 2011

Practical issues in stem cell therapy for Alzheimer's disease.

K Sugaya¹, Y D Kwak, O Ohmitsu

¹Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816. USA. ksugaya@mail.ucf.edu

Current Alzheimer Research

|October 3, 2007

Summary

Stem cell therapy shows promise for Alzheimer's disease (AD) by improving cognition and neurogenesis. Further research is needed to understand how AD pathology affects stem cells for effective treatment.

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Area of Science:

Neuroscience
Stem Cell Biology
Neurodegenerative Diseases

Background:

Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) plaques.
The role of amyloid precursor protein (APP) in neural stem cell (NSC) biology is not fully understood.
Previous studies showed potential of stem cell therapy for AD.

Purpose of the Study:

To investigate the role of APP in neural stem cell differentiation and migration.
To explore the impact of AD pathology on stem cell behavior in vivo.
To evaluate a combined approach of stem cell therapy and APP level regulation for AD treatment.

Main Methods:

In vitro studies of NSC differentiation with varying APP concentrations.
Transplantation of NSCs into APP-knockout and APP-transgenic mouse models.
In vivo assessment of NSC migration, differentiation, and neurogenesis.
Treatment with (+)-phenserine to reduce APP levels in APP-transgenic mice.

Main Results:

APP is essential for NSC differentiation and migration in vitro and in vivo.
APP overexpression promotes glial differentiation of NSCs.
Human NSC transplantation into APP-transgenic mice resulted in reduced neurogenesis and increased gliosis.
(+)-phenserine treatment enhanced neurogenesis and reduced gliosis in APP-transgenic mice.

Conclusions:

APP levels significantly regulate NSC behavior in the adult brain.
Altered APP metabolism in AD and Down syndrome may impact disease pathophysiology.
A combination therapy of stem cells and APP level modulation offers a potential treatment strategy for AD.