While previous studies have demonstrated their potential in modeling neurodegenerative diseases using RA and BDNF-driven differentiation [2–7], most existing protocols focus on general neuronal maturation or are tailored to non-tau pathologies, such as APP processing in AD [8] or dopaminergic and α-synuclein-based Parkinson’s models [9, 10]. Here, MAPT is linked to Alzheimer disease.