1. Stem Cells in the Treatment of Alzheimer’s Disease Natasha M. Delgado Literature and Bibliography

2. Background Alzheimer’s Disease Neurodegenerative disease Loss of cholinergic neurons Cognitive impairment

3. Background Stem Cells Self-renewal Differentiation Types of stem cells Embryonic Stem Cells Adult Stem Cells Neural Stem Cells Bone Marrow Stromal Cells

5. Neural Stem Cells Differentiation capabilities neurons astrocytes oligodendrocytes Exogenous neural stem cells Grafts Endogenous neural stem cells Neurotrophins Nerve Growth Factor Brain-derived neurotrophic factors Glial cell derived neurotrophic factors

6. Bone Marrow Stromal Cells Cells extracted from bone marrow Advantages Migration of cells Integration of cells into system

7. Embryonic Stem Cells Neural cells derived from embryonic stem cells Advantages Differentiate more Better Quality

8. Limitations Multifocality of Alzheimer’s Disease Route of cell administration Migration Integration Immunological response Differentiation

9. References Alzheimer’s Association. 2009 Alzheimer’s Disease Facts and Figures. 2009. Alzheimer’s & Dementia 5: 234–270 Heese K, Low JW, Inoue N. Nerve Growth Factor, Neural Stem Cells and Alzheimer’s Disease. 2006-2007 Neurosignals 15:1–12 Heikkilä TJ, Ylä-Outinen L, Tanskanen J, Lappalainen RS, Skottman H, Suuronen R, Mikkonen JE, Hyttinen JA, Narkilahti S. Human embryonic stem cell-derived neuronal cells form spontaneously active neuronal networks in vitro. 2009. Experimental Neurology 218: 109–116 Lee JK, Jin HK , Bae J. Bone marrow-derived mesenchymal stem cells reduce brain amyloid- deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. 2009. Neuroscience Letters 450: 136–141.

10. References Lerou PH, Daley GQ. Therapeutic potential of embryonic stem cells. 2005. Blood Reviews 19: 321–331. Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. 2006. Nature 441(29): 1094-1096 Pluchino S, Zanotti L, Deleidi M, Martino G. Neural stem cells and their use as therapeutic tool in neurological disorders. 2005. Brain Research Reviews 48: 211–219 Spiliotopoulos D, Goffredo D, Conti L, Di Febo F, Biella G, Toselli M, Cattaneo E. An optimized experimental strategy for efficient conversion of embryonic stem (ES)-derived mouse neural stem (NS) cells into a nearly homogeneous mature neuronal population. 2009. Neurobiology of Disease 34: 320–331. Stem Cell Basics [Internet]. [NIH] National Institutes of Health. [cited 2009]. Available from: http://stemcells.nih.gov/info/basics/

11. References Sugaya K, Brannen C.L. Stem cell strategies for neuroreplacement therapy in Alzheimer's disease. 2001. Medical Hypotheses 57(6): 697-700 Wu QY, Li J, Feng ZT, Wang TH. Bone marrow stromal cells of transgenic mice can improve the cognitive ability of an Alzheimer’s disease rat model. 2007. Neuroscience Letters 417: 281–285 Xuan AG, Luo M, Ji WD, Long DH. Effects of Engrafted Neural Stem Cells in Alzheimer’s Disease Rats. 2009. Neuroscience Letters 450:167-171. Zeng X, Rao MS. Human embryonic stem cells: long term stability, absence of senescence and a potential cells source for neural replacement. 2007. Neuroscience 145:1348-1358.