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

Control of apothecia of Sclerotinia sclerotiorum by soil amendment with S-H mixture or Perlka (R) in bean, canola and wheat fields

Ascospores of Sclerotinia sclerotiorum produced from apothecia are the primary source of inoculum for causing diseases such as white mold of common bean, pod rot of pea, stem blight of canola and head rot of sunflower and safflower in the Canadian prairies. A field study was conducted for 4 years to determine efficacy of control of production of apothecia from carpogenically germinated sclerotia of S. sclerotiorum by soil amendment with Pertka((R)) (calcium cyanamide) and S-H mixture (a formulated compound). Results of the 4-year experiments showed that amendment of soil with Perlka((R)) at low (30 g/m(2)) or high (60 g/m(2)) rate was effective in reducing carpogenic germination of sclerotia and production of apothecia under the canopy of host crops (common bean and canola) and a non-host crop (wheat). In the experiments of 1988, for example, the numbers of apothecia produced in the treatments of Perlka((R))-low rate (30 g/m(2)), Perlka((R))-high rate (60 g/m(2)) and untreated control were 42, 46, and 182 apothecia/plot (m(2)), respectively, for bean; 89, 42, and 318 apothecia/plot (m(2)), respectively, for canola; and 146, 143, and 412 apothecia/plot (m(2)), respectively, for wheat. However, soil amendment of S-H mixture at low (30 g/m(2)) or high (60 g/m(2)) rate was ineffective in reducing carpogenic germination of sclerotia and production of apothecia for all the 4 years of testing in all three crops. The ineffectiveness of S-H mixture and the practicality of Perlka((R)) for control of Sclerotinia diseases of crops grown under Canadian prairie conditions are discussed. (c) 2005 Elsevier Ltd. All rights reserved