Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

TOWARDS THE LIGHT/ TUA’R GOLEUNI: WELSH MEDIUM EDUCATION FOR THE NON-WELSH SPEAKING IN SOUTH WALES: A PARENT’S CHOICE

The Welsh-medium education system has long been seen as an effective tool of Welsh language production in Wales. The aim of this paper is to provide an overview of Welsh medium education in one south Wales Valley, ‘Cwm Rhymni / Rhymni Valley’. The main reasoning behind the primary research is to focus on the reasons why non-Welsh speaking parents chose Welsh medium education for their children. The research focuses on education but recognises the over lapping nature of the main language transmission spheres within Welsh language planning, i.e. family,community and workplace. This study adopts a mainly qualitative research strategy by administering 60 unstructured interviews to parents who chose Welsh medium nursery, primary and secondary schools for their children. However, as a secondary methodological tool, a semi-structured questionnaire was given out prior to the interviews and the interview sample was then drawn from these. Moreover, Welsh language resurgence within Anglicized areas of South Wales is a fairly unexplored field, this study is hoped to be a catalyst for many more future studies in this field and attempts to address the existing lacunae