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

Prevalence of cardiovascular risk factors in apparently healthy workers

Background: the prevalence of cardiovascular risk factors is well known in the general population. The aim of our study is to determine the prevalence of unknown major cardiovascular risk factors, in an apparently healthy Balearic working population. Method: data were obtained to 3,035 people randomly selected and with unknown previous diagnosis of hypertension, diabetes or hypercholesterolemia. To compare proportions we used the χ2 test and the t-Student test for comparison of means. Results: the prevalence of unknown hypertension in men was 20.6%, hypercholesterolemia 11.6% and 2.6% diabetes. The prevalence of unknown hypertension, hypercholesterolemia and diabetes in women were 8.3, 5.4 and 0.8%, respectively. All cardiovascular risk factors except low HDL-cholesterol were more prevalent in men. 14.4% of men and 5.5% of women met metabolic syndrome. Conclusions: there is a very high prevalence of cardiovascular risk factors in the working population considered theoretically healthy. This highlights the important role in this field from the occupational health units to make them emerge

[Prevalence of cardiovascular risk factors in Balearic workers apparently healthy].

BACKGROUND: the prevalence of cardiovascular risk factors is well known in the general population. The aim of our study is to determine the prevalence of unknown major cardiovascular risk factors, in an apparently healthy Balearic working population. METHOD: data were obtained to 3,035 people randomly selected and with unknown previous diagnosis of hypertension, diabetes or hypercholesterolemia. To compare proportions we used the χ2 test and the t-Student test for comparison of means. RESULTS: the prevalence of unknown hypertension in men was 20.6%, hypercholesterolemia 11.6%and 2.6% diabetes. The prevalence of unknown hypertension, hypercholesterolemia and diabetes in women were 8.3,5.4 and 0.8%, respectively. All cardiovascular risk factors except low HDL-cholesterol were more prevalent in men. 14.4%of men and 5.5% of women met metabolic syndrome. CONCLUSIONS: there is a very high prevalence of cardiovascular risk factors in the working population considered theoretically healthy. This highlights the important role in this field from the occupational health units to make them emerge