Stem Cell Therapies in Alzheimer's Disease: Applications for Disease Modeling

J Pharmacol Exp Ther. 2021 May;377(2):207-217. doi: 10.1124/jpet.120.000324. Epub 2021 Feb 8.


Alzheimer's disease (AD) is a neurodegenerative disease with complex pathologic and biologic characteristics. Extracellular β-amyloid deposits, such as senile plaques, and intracellular aggregation of hyperphosphorylated tau, such as neurofibrillary tangles, remain the main neuropathological criteria for the diagnosis of AD. There is currently no effective treatment of the disease, and many clinical trials have failed to prove any benefits of new therapeutics. More recently, there has been increasing interest in harnessing the potential of stem cell technologies for drug discovery, disease modeling, and cell therapies, which have been used to study an array of human conditions, including AD. The recently developed and optimized induced pluripotent stem cell (iPSC) technology is a critical platform for screening anti-AD drugs and understanding mutations that modify AD. Neural stem cell (NSC) transplantation has been investigated as a new therapeutic approach to treat neurodegenerative diseases. Mesenchymal stem cells (MSCs) also exhibit considerable potential to treat neurodegenerative diseases by secreting growth factors and exosomes, attenuating neuroinflammation. This review highlights recent progress in stem cell research and the translational applications and challenges of iPSCs, NSCs, and MSCs as treatment strategies for AD. Even though these treatments are still in relative infancy, these developing stem cell technologies hold considerable promise to combat AD and other neurodegenerative disorders. SIGNIFICANCE STATEMENT: Alzheimer's disease (AD) is a neurodegenerative disease that results in learning and memory defects. Although some drugs have been approved for AD treatment, fewer than 20% of patients with AD benefit from these drugs. Therapies based on stem cells, including induced pluripotent stem cells, neural stem cells, and mesenchymal stem cells, provide promising therapeutic strategies for AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / therapy
  • Animals
  • Drug Discovery / methods*
  • Humans
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism
  • Stem Cell Transplantation / methods*


  • Neuroprotective Agents