Here, we show that HLA HLA-DRB1*04 protects against AD, PD, and probably ALS, three prototypical neurodegenerative diseases and that HLA-DRB1*04 selectively binds the K311-acetylated epitope of the PHF6 sequence of the microtubule-associated protein tau (35), an important region in the mediation of tau aggregates. This evidence concerns the gene HLA-DRB1 and neurodegenerative disease.