Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized clinically by cognitive decline and pathologically by the development of amyloid plaques. AD is the most common cause of dementia among older people. However, there is currently no cure for AD. In this study, we aimed to elucidate the therapeutic effects of human amniotic epithelial stem cells (hAESCs) in a transgenic mouse model of AD. Tg2576 transgenic (Tg) mice underwent behavioral tests, namely the Morris water maze and Y-maze tests, to assess their cognitive function. In the Morris water maze test, hAESC-treated Tg mice exhibited significantly shorter escape latencies than vehicle-treated Tg mice. In the Y-maze test, hAESC-treated Tg mice exhibited significantly higher rate of spontaneous alteration than vehicle-treated Tg mice, while the total number of arm entries did not differ between the groups. Furthermore, Congo red staining revealed that hAESCs injection reduced the number of amyloid plaques present in the brains of Tg mice. Finally, beta-secretase (BACE) activity was significantly decreased in Tg mice at 60 min after hAESCs injection. In this study, we found that intracerebral injection of hAESCs alleviated cognitive impairment in a Tg2576 mouse model of AD. Our results indicate that hAESCs injection reduced amyloid plaques caused by reduced BACE activity. These results indicate that hAESCs may be a useful therapeutic agent for the treatment of AD-related memory impairment.

Highlights

  • Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by memory loss and cognitive decline sufficient to interfere with daily life

  • We demonstrated that a reduction in BACE activity may be the mechanism by which human amniotic epithelial stem cells (hAESCs) transplantation reduces the number of amyloid plaques in Tg2576 transgenic mice

  • With approval from the Institutional Review Board of Seoul National University (IRB No C-0809-009-255), hAESCs at passage 3 were provided by the Stem Cell Research Institute of Biostar Inc. (Seoul, Republic of Korea)

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Summary

Introduction

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by memory loss and cognitive decline sufficient to interfere with daily life. Transplantation of hAESCs Reduces Amyloid Burden in Tg2576 Alzheimer’s Disease Transgenic Mice. Beta-secretase (BACE) activity was assessed to understand the mechanism underlying the hAESCs transplantation-induced reduction in amyloid plaques number in Tg2576 mice. When exposed to exogenous growth factors, hAESCs are able to differentiate into cells of the ectoderm, mesoderm, and endoderm They have therapeutic potential for treating various diseases of the skin, liver, kidneys, musculoskeletal system, and central nervous system [8,14,18,19]. HAESCs improved spatial memory in double-transgenic mice by increasing acetylcholine levels and promoting the survival of cholinergic neurites in the hippocampus [24]. We demonstrated that a reduction in BACE activity may be the mechanism by which hAESCs transplantation reduces the number of amyloid plaques in Tg2576 transgenic mice. We believe that hAESCs may be a useful therapeutic agent for the treatment of AD-related memory impairment

Animals
Preparation of hAESCs
Behavioral Tests
Collection of Brain Tissue
Congo Red Staining
BACE Activity
Findings
Statistical Analysis
Full Text
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