{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:00:44Z","timestamp":1791342044639,"version":"4.3.1"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Emerging evidence implicates a role for neuroinflammation in Alzheimer disease (AD) pathogenesis, predominantly involving the innate immune system. Blood leukocyte counts are easily accessible markers of immune function; however, their association with the risk of AD is unknown.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate the observational and genetic associations between types of blood leukocytes and risk of AD.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In a cohort study comprising observational and genetic analyses, the Copenhagen General Population Study prospective cohort (n\u2009=\u2009101\u202f582) was used for the observational analyses. For the genetic studies, nonlinearity was first evaluated for the association between leukocyte cell counts and AD risk using individual-level data from the UK Biobank (n\u2009=\u2009365\u202f913). Subsequently, a 2-sample mendelian randomization framework was applied using genetic instruments for blood leukocyte counts (n\u2009=\u2009563 085); for AD, the European Alzheimer &amp;amp; Dementia Biobank was used, including 85\u202f934 individuals with AD and 401\u202f577 controls and the International Genomics of Alzheimer\u2019s Project, including 21\u202f982 individuals with AD and 41\u202f944 controls.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Observational and genetically determined types of blood leukocyte counts.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Hazard ratios (HRs) and 95% CIs for AD of cell count percentile groups in observational studies and odds ratios (ORs) and 95% CIs for AD per 1 SD genetically determined cell counts.<\/jats:p><\/jats:sec>Results<\/jats:title>This cohort study included 101\u202f582 participants (55 891 [55.0%] women) with a median age of 58 years (IQR, 48-67 years); of these, 1588 individuals developed AD. Multivariable-adjusted HRs for participants in the less than 5th vs the 25th to 75th (reference) percentile group were 1.24 (95% CI, 0.99-1.54) for blood monocytes and 1.25 for blood eosinophils (95% CI, 1.05-1.50). For participants in the greater than 95th vs the 25th to 75th percentile group, the HR was 1.30 (95% CI, 1.06-1.61) for blood neutrophils. Genetically, no evidence favored possible nonlinear associations. The ORs for AD per 1-SD decrease in genetically determined blood monocytes were 1.04 (95% CI, 1.00-1.10) in the European Alzheimer &amp;amp; Dementia Biobank consortium and 1.09 (95% CI, 1.01-1.17) in the International Genomics of Alzheimer\u2019s Project consortium. Using mendelian randomization, sensitivity analyses and multivariable analysis showed similar results.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The findings of this study suggest that low blood monocyte counts are associated with increased AD risk. These findings highlight a potential role of the innate immune system in AD pathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2022.35648","type":"journal-article","created":{"date-parts":[[2022,10,10]],"date-time":"2022-10-10T15:23:08Z","timestamp":1665415388000},"page":"e2235648","source":"Crossref","is-referenced-by-count":35,"title":["Blood Leukocyte Counts in Alzheimer Disease"],"prefix":"10.1001","volume":"5","author":[{"given":"Jiao","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Copenhagen University Hospital\u2013Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands"},{"name":"Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper 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