SPI1 and Alzheimer disease: This is in agreement with data showing that elevated TNF-α is a hallmark of several neurodegenerative diseases, including AD, and can promote chronic neuroinflammation and synaptic dysfunction, when unchecked {Heneka, 2015} {Heppner, 2015} and numerous data showing that PU.1 drives, amongst other genes, Tnf-α expression in the context of neurodegenerative diseases {Ralvenius, 2024} {Xu, 2025}.