Over 55 million people worldwide live with dementia due to neurodegenerative diseases such as Alzheimer´s disease (AD) and frontotemporal dementia (FTD), creating a significant socio-economic burden due to the lack of disease-modifying therapies. Over 80 genetic variants influencing AD, FTD, and other neurodegenerative diseases, with many linked to genes regulating the endolysosomal system, including granulin (GRN). Protein progranulin (PGRN), encoded by GRN gene, controls vital cellular functions in neuron and microglia. But the mechanisms by which PGRN loss leads to neural dysfunction and dementia remain unclear, with most insights coming from animal studies. I use human cortical-like neural organoids with GRN mutations to explore PGRN's role in neuronal dysfunction and microglia-neuron interactions. I hypothesize that lysosomal disruptions due to loss in PGRN lead to synaptic deficits, altering the balance of neuronal excitation/inhibition and thus contributing to neurodegeneration

2026

2030