| Background:Alzheimer’s disease(AD),the most prevalent form of dementia,is one of the public health challenges in the 21 st century.Inflammation plays a role in occurrence and progression of AD.Whether peripheral immune cells are involved in major pathological processes including β-amyloid plaques and tau tangles is still controversial.Thus,we aimed to examine whether peripheral immune cells counts were associated with early changes in cerebrospinal fluid(CSF)biomarkers of AD pathology in cognitively intact older adults.Methods:This study included 738 objective cognitive normal participants from the Chinese Alzheimer’s Biomarker and Lifestyle(CABLE)database.CSF β-amyloid 42(Aβ42),phosphorylated tau protein(p-tau)and total tau protein(t-tau)were used to reflect AD pathology.CSF biomarker positive participants were defined as having CSF Aβ42 levels in the lower one-third of the distribution of participants(A+: ≤121.17pg/m L)or having p-tau(T+: ≥39.02pg/m L)or t-tau(N+: ≥181.19pg/m L)levels in the upper one-third of the distribution.Group comparisons of peripheral immune cells counts were tested using the analysis of covariance.The multivariate linear regression analyses were performed to determine the associations between immune cells counts and CSF biomarkers of AD pathology.We used logistic regression to examine the associations of immune cells counts with risks of incident preclinical AD.We used mediation analysis to test whether the relationships of peripheral immune cells with subjective cognitive dysfunction(SCD)were mediated by AD pathologies.For all regression models,we used the variance inflation factor(VIF)to explore multicollinearity.A two-tailed P < 0.05 was considered statistically significant.Results:There were relationships between Aβ deposition and lymphocytes and eosinophils.In ATN biological construct,lymphocyte percentage(LY%)were significantly decreased in A+(p = 0.0093)and A+T+(p = 0.0022)subgroup compared with A-and A-T-subgroup.In contrast,eosinophil count(EO)and eosinophil percentage(EO%)were significantly raised in A+T+ subgroup(EO,p = 0.0045;EO%,p = 0.0394).Furthermore,EO was increased in A+ subgroup compared to A-subgroup(p = 0.0294).The differences in cells counts were also compared between stage 0,stage 1,and stage 2.There were decreased trends in LY%(p = 0.0122),and increased trends in EO(p = 0.0118)and EO%(p =0.0436).Decreased lymphocytes and increased eosinophils were significantly correlated with elevated brain Aβ burden.LY% was significantly associated with CSF Aβ42(β =0.0990,p = 0.0092)and CSF p-tau/Aβ42(β =-0.0805,p = 0.0311),and moderately associated with CSF Aβ42/40(β =-0.0805,p = 0.0311).There were negative associations of EO with Aβ42(β =-0.0900,p = 0.0186)and Aβ42/40(β =-0.0849,p = 0.0253),and positive associations with p-tau/Aβ42(β = 0.0861,p = 0.0223)and t-tau/Aβ42(β =0.0894,p = 0.0164).EO% was significantly associated with p-tau/Aβ42(β = 0.0766,p =0.0415),and moderately associated with CSF Aβ42(β =-0.0718,p = 0.0598)and t-tau/Aβ42(β = 0.0691,p = 0.0626).Increased incidence rate of preclinical AD was observed with improved levels of eosinophils and reduced levels of lymphocytes(LY%,OR = 0.95;EO,OR = 1.05).The eosinophil-to-lymphocyte ratio(ELR)was used to reflect the overall role of peripheral immune cells.We found an association between ELR and incident SCD(β = 0.0377,p = 0.0412).Mediation analyses showed that this association was partly mediated by Aβ pathology Conclusion:In summary,our study showed that peripheral lymphocytes and eosinophils were associated with Aβ pathology and incident preclinical AD.And Aβ pathology played a role in the relationship between peripheral immune cells and incident SCD.The results of this study provided evidence that peripheral immune cells play roles in AD pathology at preclinical stages.This study may help us to understand the pathogenic and regulatory pathways in AD,and develop therapeutic strategies. |
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