SP2 is also found to be lead relevant because lead substitution in Sp1 could cause the upregulation of APP transcription, then cause the build-up of Aβ in the brain and contribute to AD, and it has been known that the Sp-family of TFs (Sp1, Sp2, Sp3, and Sp4) regulate the same genes85. Here, SP4 is linked to Alzheimer disease.