Cargando…

Blood Leukocyte Counts in Alzheimer Disease

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. OBJECTIV...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Jiao, Thomassen, Jesper Qvist, Nordestgaard, Børge G., Tybjærg-Hansen, Anne, Frikke-Schmidt, Ruth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552891/
https://www.ncbi.nlm.nih.gov/pubmed/36215071
http://dx.doi.org/10.1001/jamanetworkopen.2022.35648
_version_ 1784806349147734016
author Luo, Jiao
Thomassen, Jesper Qvist
Nordestgaard, Børge G.
Tybjærg-Hansen, Anne
Frikke-Schmidt, Ruth
author_facet Luo, Jiao
Thomassen, Jesper Qvist
Nordestgaard, Børge G.
Tybjærg-Hansen, Anne
Frikke-Schmidt, Ruth
author_sort Luo, Jiao
collection PubMed
description 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 = 101 582) 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 = 365 913). 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 85 934 individuals with AD and 401 577 controls and the International Genomics of Alzheimer’s Project, including 21 982 individuals with AD and 41 944 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 101 582 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.
format Online
Article
Text
id pubmed-9552891
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher American Medical Association
record_format MEDLINE/PubMed
spelling pubmed-95528912022-10-26 Blood Leukocyte Counts in Alzheimer Disease Luo, Jiao Thomassen, Jesper Qvist Nordestgaard, Børge G. Tybjærg-Hansen, Anne Frikke-Schmidt, Ruth JAMA Netw Open Original Investigation 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 = 101 582) 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 = 365 913). 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 85 934 individuals with AD and 401 577 controls and the International Genomics of Alzheimer’s Project, including 21 982 individuals with AD and 41 944 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 101 582 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. American Medical Association 2022-10-10 /pmc/articles/PMC9552891/ /pubmed/36215071 http://dx.doi.org/10.1001/jamanetworkopen.2022.35648 Text en Copyright 2022 Luo J et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Luo, Jiao
Thomassen, Jesper Qvist
Nordestgaard, Børge G.
Tybjærg-Hansen, Anne
Frikke-Schmidt, Ruth
Blood Leukocyte Counts in Alzheimer Disease
title Blood Leukocyte Counts in Alzheimer Disease
title_full Blood Leukocyte Counts in Alzheimer Disease
title_fullStr Blood Leukocyte Counts in Alzheimer Disease
title_full_unstemmed Blood Leukocyte Counts in Alzheimer Disease
title_short Blood Leukocyte Counts in Alzheimer Disease
title_sort blood leukocyte counts in alzheimer disease
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552891/
https://www.ncbi.nlm.nih.gov/pubmed/36215071
http://dx.doi.org/10.1001/jamanetworkopen.2022.35648
work_keys_str_mv AT luojiao bloodleukocytecountsinalzheimerdisease
AT thomassenjesperqvist bloodleukocytecountsinalzheimerdisease
AT nordestgaardbørgeg bloodleukocytecountsinalzheimerdisease
AT tybjærghansenanne bloodleukocytecountsinalzheimerdisease
AT frikkeschmidtruth bloodleukocytecountsinalzheimerdisease