期刊
NATURE AGING
卷 2, 期 10, 页码 956-+出版社
SPRINGERNATURE
DOI: 10.1038/s43587-022-00293-x
关键词
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资金
- Wellcome Trust [221854/Z/20/Z]
- UK Medical Research Council [S011676, R024227, MR/S011676, MR/R024227]
- Business Finland [HUS 4685/31/2016, UH 4386/31/2016]
- AbbVie Inc.
- AstraZeneca UK Ltd
- Biogen MA Inc.
- Bristol Myers Squibb (Celgene Corporation)
- Bristol Myers Squibb (Celgene International II Sarl)
- Genentech Inc.
- Merck Sharp Dohme Corp.
- Pfizer Inc.
- GlaxoSmithKline Intellectual Property Development Ltd.
- Sanofi US Services Inc.
- Maze Therapeutics Inc.
- Janssen Biotech Inc.
- Novartis AG
- Boehringer Ingelheim
- National Institute on Aging (National Institutes of Health) [R01AG056477, RF1AG062553]
- British Heart Foundation [RG/16/11/32334]
- SomaLogic, Inc.
- Academy of Finland [339568, 331671, 285380, 312062, 311492, 350426]
- Paivikki and Sakari Sohlberg foundation
- Emil Aaltonen Foundation
- University College London Hospitals' National Institute for Health Research (NIHR) Biomedical Research Centre
- North Thames NIHR Applied Research Collaboration
- UCL British Heart Foundation Accelerator [AA/18/6/34223]
- UCL NIHR Biomedical Research Centre
- UKRI/NIHR [MR/V033867/1]
- Sigrid Juselius Foundation
- University of Helsinki HiLIFE Fellow grant [2017-2020]
- US National Institute on Aging [R01AG056477, R01AG062553]
- NordForsk [75021]
- Helsinki Institute of Life Science [H970]
- Finnish Work Environment Fund [190424]
- Academy of Finland (AKA) [312062] Funding Source: Academy of Finland (AKA)
This study suggests that autoimmunity may play a modifiable role in diseases causing dementia, based on converging results from different lines of human research. Immune system dysfunction and blood-brain barrier dysfunction are implicated in the development of dementia-causing diseases, but their causal role remains unknown.
Immune system dysfunction has been implicated in the development of dementias, but its causal role remains unknown. Providing converging results from different lines of human research, this study by Lindbohm et al. suggests that autoimmunity may be a modifiable component in diseases causing dementia. Immune system and blood-brain barrier dysfunction are implicated in the development of Alzheimer's and other dementia-causing diseases, but their causal role remains unknown. We performed Mendelian randomization for 1,827 immune system- and blood-brain barrier-related biomarkers and identified 127 potential causal risk factors for dementia-causing diseases. Pathway analyses linked these biomarkers to amyloid-beta, tau and alpha-synuclein pathways and to autoimmunity-related processes. A phenome-wide analysis using Mendelian randomization-based polygenic risk score in the FinnGen study (n = 339,233) for the biomarkers indicated shared genetic background for dementias and autoimmune diseases. This association was further supported by human leukocyte antigen analyses. In inverse-probability-weighted analyses that simulate randomized controlled drug trials in observational data, anti-inflammatory methotrexate treatment reduced the incidence of Alzheimer's disease in high-risk individuals (hazard ratio compared with no treatment, 0.64, 95% confidence interval 0.49-0.88, P = 0.005). These converging results from different lines of human research suggest that autoimmunity is a modifiable component in dementia-causing diseases.
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