Evaluation of neuroinflammation and therapeutic approaches in iPSC derived neuron and microglia co-culture containing PSEN1 Alzheimer's mutation

• Grant number: 24/22615-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: November 28, 2025
• End date: November 27, 2026
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Merari de Fátima Ramires Ferrari
• Grantee: Luísa Machado Pinheiro
• Supervisor: Alysson Renato Muotri
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 22/12697-5 - Evaluation of neuroinflammation, dynamic of synapses and interaction between organelles in cell model of Alzheimer's Disease, BP.DD

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive cognitive and behavioral impairments, affecting millions of people worldwide, with numbers expected to increase significantly as the global population ages. Neuroinflammation plays a critical role in AD progression, with microglia being central to the inflammatory response. Overactivation of microglia contributes to neuronal dysfunction and synaptic loss, which are key features of AD. While numerous models, such as post-mortem brain samples, cell lines, and animal models, have been used to study AD, these systems have limitations. In this regard, we will develop a model based on induced pluripotent stem cells (iPSCs), which enable patient-specific models and thus offer a more accurate representation of the disease. Specifically, we will use co-cultures of iPSC-derived microglia and cholinergic neurons to investigate cellular interactions relevant to Alzheimer's disease (AD). Additionally, by utilizing CRISPR-Cas9 gene editing to introduce the PSEN1 mutation associated with AD, we aim to achieve precise genetic modeling of the disease, enhancing the relevance of this system for studying disease mechanisms.Following the establishment of this model, we will assess the microglial response under control conditions and investigate the potential therapeutic effects of natural compounds such as Andiroba and Guaraná, compounds that have shown promising results and may offer new avenues for modulating neuroinflammation in AD. This approach holds the potential to advance our understanding of AD pathogenesis and provide new therapeutic strategies to mitigate neuroinflammation and slow disease progression.