Induced pluripotent stem cell-derived neural precursors improve memory, synaptic and pathological abnormalities in a mouse model of alzheimer’s disease

Enrique Armijo, George Edwards, Andrea Flores, Jorge Vera, Mohammad Shahnawaz, Fabio Moda, Cesar Gonzalez, Magdalena Sanhueza, Claudio Soto

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

Original languageEnglish (US)
Article number1802
JournalCells
Volume10
Issue number7
DOIs
StatePublished - Jul 2021
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Amyloid-beta
  • Clinical symptoms
  • Inflammation
  • Stem cells
  • Tau
  • Therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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