Association between neutrophil to lymphocyte ratio and Alzheimer's disease in large biobank cohorts

BackgroundNeutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.ObjectiveThe objective of this study is to assess the association between NLR and AD as...

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Published in:Journal of Alzheimer's disease Vol. 108; no. 3; p. 1302
Main Authors: Drzymalla, Emily, Avery, Christy, Palta, Priya, Reiner, Alexander P, Sun, Quan, Raffield, Laura M
Format: Journal Article
Language:English
Published: United States 01.12.2025
Subjects:
Aged
Aged, 80 and over
Alzheimer Disease - blood
Alzheimer Disease - genetics
Alzheimer Disease - immunology
Biological Specimen Banks
Biomarkers - blood
Cohort Studies
Female
Humans
Lymphocytes
Male
Mendelian Randomization Analysis
Middle Aged
Neutrophils
United Kingdom - epidemiology
United Kingdom
neutrophil to lymphocyte ratio
Mendelian randomization
inflammation
Alzheimer's disease
biobank
ISSN:1875-8908, 1875-8908
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Abstract BackgroundNeutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.ObjectiveThe objective of this study is to assess the association between NLR and AD as a biomarker or potential causal step for AD pathogenesis.MethodsCohorts used for analysis include the UK Biobank (n = 207100; n = 2198 AD cases) and the All of Us research program (AoU, n = 45202; n = 263 AD cases) which allowed for a larger sample size than most previous studies. Cox proportional hazard models were used to assess the association between NLR and AD, including in models adjusting for factors in the UK Biobank Dementia Risk Score. A Mendelian randomization analysis was performed to assess the potential causality between NLR and AD.ResultsNLR was associated with AD in the UK Biobank (HR: 1.03 per 1 SD, 95% CI: 1.01-1.05) but not in AoU (HR: 1.02, 95% CI: 0.92-1.14). A fixed effects model resulted in a pooled HR: 1.03 (95% CI: 1.02-1.05). These effects were robust to adjustment for C-reactive protein, ε4 genotype status, ε2 genotype status, and other AD risk factors. The MR analysis was performed with 214 NLR-associated variants but was not significant (IVW estimate: -0.001, p: 0.99).ConclusionsFindings provide evidence for NLR as a biomarker for AD but not as a causal risk factor.
AbstractList BackgroundNeutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.ObjectiveThe objective of this study is to assess the association between NLR and AD as a biomarker or potential causal step for AD pathogenesis.MethodsCohorts used for analysis include the UK Biobank (n = 207100; n = 2198 AD cases) and the All of Us research program (AoU, n = 45202; n = 263 AD cases) which allowed for a larger sample size than most previous studies. Cox proportional hazard models were used to assess the association between NLR and AD, including in models adjusting for factors in the UK Biobank Dementia Risk Score. A Mendelian randomization analysis was performed to assess the potential causality between NLR and AD.ResultsNLR was associated with AD in the UK Biobank (HR: 1.03 per 1 SD, 95% CI: 1.01-1.05) but not in AoU (HR: 1.02, 95% CI: 0.92-1.14). A fixed effects model resulted in a pooled HR: 1.03 (95% CI: 1.02-1.05). These effects were robust to adjustment for C-reactive protein, APOE ε4 genotype status, APOE ε2 genotype status, and other AD risk factors. The MR analysis was performed with 214 NLR-associated variants but was not significant (IVW estimate: -0.001, p: 0.99).ConclusionsFindings provide evidence for NLR as a biomarker for AD but not as a causal risk factor.BackgroundNeutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.ObjectiveThe objective of this study is to assess the association between NLR and AD as a biomarker or potential causal step for AD pathogenesis.MethodsCohorts used for analysis include the UK Biobank (n = 207100; n = 2198 AD cases) and the All of Us research program (AoU, n = 45202; n = 263 AD cases) which allowed for a larger sample size than most previous studies. Cox proportional hazard models were used to assess the association between NLR and AD, including in models adjusting for factors in the UK Biobank Dementia Risk Score. A Mendelian randomization analysis was performed to assess the potential causality between NLR and AD.ResultsNLR was associated with AD in the UK Biobank (HR: 1.03 per 1 SD, 95% CI: 1.01-1.05) but not in AoU (HR: 1.02, 95% CI: 0.92-1.14). A fixed effects model resulted in a pooled HR: 1.03 (95% CI: 1.02-1.05). These effects were robust to adjustment for C-reactive protein, APOE ε4 genotype status, APOE ε2 genotype status, and other AD risk factors. The MR analysis was performed with 214 NLR-associated variants but was not significant (IVW estimate: -0.001, p: 0.99).ConclusionsFindings provide evidence for NLR as a biomarker for AD but not as a causal risk factor.
BackgroundNeutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune activation in Alzheimer's disease (AD) pathogenesis.ObjectiveThe objective of this study is to assess the association between NLR and AD as a biomarker or potential causal step for AD pathogenesis.MethodsCohorts used for analysis include the UK Biobank (n = 207100; n = 2198 AD cases) and the All of Us research program (AoU, n = 45202; n = 263 AD cases) which allowed for a larger sample size than most previous studies. Cox proportional hazard models were used to assess the association between NLR and AD, including in models adjusting for factors in the UK Biobank Dementia Risk Score. A Mendelian randomization analysis was performed to assess the potential causality between NLR and AD.ResultsNLR was associated with AD in the UK Biobank (HR: 1.03 per 1 SD, 95% CI: 1.01-1.05) but not in AoU (HR: 1.02, 95% CI: 0.92-1.14). A fixed effects model resulted in a pooled HR: 1.03 (95% CI: 1.02-1.05). These effects were robust to adjustment for C-reactive protein, ε4 genotype status, ε2 genotype status, and other AD risk factors. The MR analysis was performed with 214 NLR-associated variants but was not significant (IVW estimate: -0.001, p: 0.99).ConclusionsFindings provide evidence for NLR as a biomarker for AD but not as a causal risk factor.
Author Reiner, Alexander P
Drzymalla, Emily
Avery, Christy
Raffield, Laura M
Sun, Quan
Palta, Priya
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Mendelian randomization
inflammation
Alzheimer's disease
biobank
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Snippet BackgroundNeutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker for chronic disease that also may provide evidence for peripheral innate immune...
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SubjectTerms Aged
Aged, 80 and over
Alzheimer Disease - blood
Alzheimer Disease - genetics
Alzheimer Disease - immunology
Biological Specimen Banks
Biomarkers - blood
Cohort Studies
Female
Humans
Lymphocytes
Male
Mendelian Randomization Analysis
Middle Aged
Neutrophils
United Kingdom - epidemiology
Title Association between neutrophil to lymphocyte ratio and Alzheimer's disease in large biobank cohorts
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