Blood Leukocyte Counts in Alzheimer Disease

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Blood Leukocyte Counts in Alzheimer Disease. / Luo, Jiao; Thomassen, Jesper Qvist; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Frikke-Schmidt, Ruth.

In: JAMA network open, Vol. 5, No. 10, E2235648, 2022.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Luo, J, Thomassen, JQ, Nordestgaard, BG, Tybjærg-Hansen, A & Frikke-Schmidt, R 2022, 'Blood Leukocyte Counts in Alzheimer Disease', JAMA network open, vol. 5, no. 10, E2235648. https://doi.org/10.1001/jamanetworkopen.2022.35648

APA

Luo, J., Thomassen, J. Q., Nordestgaard, B. G., Tybjærg-Hansen, A., & Frikke-Schmidt, R. (2022). Blood Leukocyte Counts in Alzheimer Disease. JAMA network open, 5(10), [E2235648]. https://doi.org/10.1001/jamanetworkopen.2022.35648

Vancouver

Luo J, Thomassen JQ, Nordestgaard BG, Tybjærg-Hansen A, Frikke-Schmidt R. Blood Leukocyte Counts in Alzheimer Disease. JAMA network open. 2022;5(10). E2235648. https://doi.org/10.1001/jamanetworkopen.2022.35648

Author

Luo, Jiao ; Thomassen, Jesper Qvist ; Nordestgaard, Børge G. ; Tybjærg-Hansen, Anne ; Frikke-Schmidt, Ruth. / Blood Leukocyte Counts in Alzheimer Disease. In: JAMA network open. 2022 ; Vol. 5, No. 10.

Bibtex

@article{c4f9ba0e9bcb40ea8188e6b678fe2894,
title = "Blood Leukocyte Counts in Alzheimer Disease",
abstract = "Importance: 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. Objective: To investigate the observational and genetic associations between types of blood leukocytes and risk of AD. Design, Setting, and Participants: In a cohort study comprising observational and genetic analyses, the Copenhagen General Population Study prospective cohort (n = 101582) 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 = 365913). Subsequently, a 2-sample mendelian randomization framework was applied using genetic instruments for blood leukocyte counts (n = 563 085); for AD, the European Alzheimer & Dementia Biobank was used, including 85934 individuals with AD and 401577 controls and the International Genomics of Alzheimer's Project, including 21982 individuals with AD and 41944 controls. Exposures: Observational and genetically determined types of blood leukocyte counts. Main Outcomes and Measures: 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. Results: This cohort study included 101582 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 & Dementia Biobank consortium and 1.09 (95% CI, 1.01-1.17) in the International Genomics of Alzheimer's Project consortium. Using mendelian randomization, sensitivity analyses and multivariable analysis showed similar results. Conclusions and Relevance: 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..",
author = "Jiao Luo and Thomassen, {Jesper Qvist} and Nordestgaard, {B{\o}rge G.} and Anne Tybj{\ae}rg-Hansen and Ruth Frikke-Schmidt",
note = "Publisher Copyright: {\textcopyright} 2022 American Medical Association. All rights reserved.",
year = "2022",
doi = "10.1001/jamanetworkopen.2022.35648",
language = "English",
volume = "5",
journal = "JAMA network open",
issn = "2574-3805",
publisher = "American Medical Association",
number = "10",

}

RIS

TY - JOUR

T1 - Blood Leukocyte Counts in Alzheimer Disease

AU - Luo, Jiao

AU - Thomassen, Jesper Qvist

AU - Nordestgaard, Børge G.

AU - Tybjærg-Hansen, Anne

AU - Frikke-Schmidt, Ruth

N1 - Publisher Copyright: © 2022 American Medical Association. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Importance: 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. Objective: To investigate the observational and genetic associations between types of blood leukocytes and risk of AD. Design, Setting, and Participants: In a cohort study comprising observational and genetic analyses, the Copenhagen General Population Study prospective cohort (n = 101582) 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 = 365913). Subsequently, a 2-sample mendelian randomization framework was applied using genetic instruments for blood leukocyte counts (n = 563 085); for AD, the European Alzheimer & Dementia Biobank was used, including 85934 individuals with AD and 401577 controls and the International Genomics of Alzheimer's Project, including 21982 individuals with AD and 41944 controls. Exposures: Observational and genetically determined types of blood leukocyte counts. Main Outcomes and Measures: 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. Results: This cohort study included 101582 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 & Dementia Biobank consortium and 1.09 (95% CI, 1.01-1.17) in the International Genomics of Alzheimer's Project consortium. Using mendelian randomization, sensitivity analyses and multivariable analysis showed similar results. Conclusions and Relevance: 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..

AB - Importance: 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. Objective: To investigate the observational and genetic associations between types of blood leukocytes and risk of AD. Design, Setting, and Participants: In a cohort study comprising observational and genetic analyses, the Copenhagen General Population Study prospective cohort (n = 101582) 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 = 365913). Subsequently, a 2-sample mendelian randomization framework was applied using genetic instruments for blood leukocyte counts (n = 563 085); for AD, the European Alzheimer & Dementia Biobank was used, including 85934 individuals with AD and 401577 controls and the International Genomics of Alzheimer's Project, including 21982 individuals with AD and 41944 controls. Exposures: Observational and genetically determined types of blood leukocyte counts. Main Outcomes and Measures: 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. Results: This cohort study included 101582 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 & Dementia Biobank consortium and 1.09 (95% CI, 1.01-1.17) in the International Genomics of Alzheimer's Project consortium. Using mendelian randomization, sensitivity analyses and multivariable analysis showed similar results. Conclusions and Relevance: 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..

U2 - 10.1001/jamanetworkopen.2022.35648

DO - 10.1001/jamanetworkopen.2022.35648

M3 - Journal article

C2 - 36215071

AN - SCOPUS:85139572618

VL - 5

JO - JAMA network open

JF - JAMA network open

SN - 2574-3805

IS - 10

M1 - E2235648

ER -

ID: 327331093