Induced-pluripotent stem cell-derived immunotherapy for Tau and Alzheimer's disease

Adv Protein Chem Struct Biol. 2026:151:197-224. doi: 10.1016/bs.apcsb.2025.10.005. Epub 2025 Nov 4.

Abstract

Neurodegenerative diseases, such as Alzheimer's disease, are characterized by progressive neuronal death and functional decline. Key pathological hallmarks of Alzheimer's disease include the deposition of aggregated amyloid-β (Aβ) proteins into extracellular plaques and the accumulation of hyperphosphorylated Tau protein into intracellular aggregates. These toxic species triggers neuroinflammation through interactions with glial cells, further exacerbating neurodegeneration. This study explores the potential of induced pluripotent stem cells (iPSCs) in disease modelling, focusing on their application in modelling Alzheimer's disease pathology and therapeutic screening. Additionally, the development of advanced 3D culture systems and organoids offers insights into human-specific Alzheimer's disease mechanisms, overcoming limitations of traditional 2D and animal models. The focus is on the role of microglial polarization in neuroinflammation and its potential therapeutic modulation, offering a promising approach for the treatment of neurodegenerative diseases.

Keywords: Alzheimer’s disease; Induced pluripotent stem cells; Neuroinflammation; Organoids; Tau.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / immunology
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Alzheimer Disease* / therapy
  • Animals
  • Humans
  • Immunotherapy*
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / immunology
  • Induced Pluripotent Stem Cells* / metabolism
  • tau Proteins* / immunology
  • tau Proteins* / metabolism

Substances

  • tau Proteins