Modeling Alzheimer's Disease Using Human Brain Organoids

Methods Mol Biol. 2023:2561:135-158. doi: 10.1007/978-1-0716-2655-9_7.

Abstract

Alzheimer's disease (AD) is the primary cause of dementia, to date. The urgent need to understand the biological and biochemical processes related to this condition, as well as the demand for reliable in vitro models for drug screening, has led to the development of novel techniques, among which stem cell methods are of utmost relevance for AD research, particularly the development of human brain organoids. Brain organoids are three-dimensional cellular aggregates derived from induced pluripotent stem cells (iPSCs) that recreate different neural cell interactions and tissue characteristics in culture. Here, we describe the protocol for the generation of brain organoids derived from AD patients and for the analysis of AD-derived pathology. AD organoids can recapitulate beta-amyloid and tau pathological features, making them a promising model for studying the molecular mechanisms underlying disease and for in vitro drug testing.

Keywords: Alzheimer’s disease; Amyloidosis; Brain organoids; Induced pluripotent stem cells; Tauopathies; neurodegenerative diseases.

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Brain / pathology
  • Humans
  • Induced Pluripotent Stem Cells*
  • Organoids

Substances

  • Amyloid beta-Peptides