Protective HLA-DRB1*04<\/em> subtypes bind strongly to aggregation-prone tau PHF6 sequence when acetylated at K311<\/p>\n<\/h3>\n By Elana Gotkine HealthDay Reporter<\/b><\/p>\n <\/b><\/p>\n FRIDAY, Sept. 8, 2023 (HealthDay News) — Alzheimer disease (AD) and Parkinson disease (PD) share the same protective association at the human leukocyte antigen (HLA) locus, according to a study published online Aug. 29 in the Proceedings of the National Academy of Sciences<\/em>.<\/p>\n Yann Le Guen, Ph.D., from Stanford University in California, and colleagues examined HLA associations in more than 176,000 individuals with PD and AD compared to controls across multiancestry groups.<\/p>\n The researchers found that the diseases shared the same protective association at the HLA locus. The association was best accounted for by the hierarchical protective effects of HLA-DRB1*04<\/em> subtypes, which were strongest with HLA-DRB1*04:04<\/em> and HLA-DRB1*04:07<\/em> and intermediate with HLA-DRB1*04:01<\/em> and HLA-DRB1*04:03<\/em>. In postmortem brains, the same signal was associated with reduced neurofibrillary tangles; the signal was also associated with reduced tau levels in cerebrospinal fluid and with increased A\u00ce\u00b242 to a lesser extent. When acetylated at a lysine (K311), protective HLA-DRB1*04<\/em> subtypes strongly bound the aggregation-prone tau PHF6 sequence.<\/p>\n “Our results also open the possibility that targeting tau epitopes containing acetylated-K311 through chimeric antigen receptor T cells or antibodies could have therapeutic values,” the authors write.<\/p>\n Two authors filed a patent application on this discovery.<\/p>\n