Citations 3
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
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Proceedings of the National Academy of Sciences | August 29, 2023 | Volume: 120 | Issue: 36 | Pages: No page available
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.
Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society
Lennep, Jeanine E. Roeters van , Tokgözoğlu, Lâle , Badimón, Lina , Dumanski, Sandra M. , Gulati, Martha , Hess, Connie N. , Holven, Kirsten B. , Kavousi, Maryam , Kayıkçıoğlu, Meral , Lutgens, Esther , Stock, Jane K., Tybjærg‐Hansen, Anne, Benn, Marianne , Roeters van Lennep, Jeanine E , Michos, Erin D , Prescott, Eva , Wermer, Marieke J H , Benn, Marianne , Lutgens, Esther , Kavousi, Maryam , Michos, Erin D.
European Heart Journal | July 26, 2023 | Volume: 44 | Issue: 39 | Pages: 4157-4173
Abstract Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.
The Dynamic and Multifaceted Nature of Cardiovascular Disease and Using Genetic Testing to Inform Clinical Care: An International Perspective
Baudhuin, Linnea M. , Backer, Julie De , Ingles, Jodie , Tybjærg‐Hansen, Anne, De Backer, Julie F A , Ingles, Jodie , Milewicz, Dianna M.
Clinical Chemistry | October 28, 2020 | Volume: 67 | Issue: 1 | Pages: 33-40