The impact of inflammation on plasma biomarkers of Alzheimer’s Disease

Abstract

AbstractBackgroundPlasma biomarkers of Alzheimer’s disease have been proposed as less expensive, less invasive and readily scalable biomarkers for use as diagnostic biomarkers, predictors of risk and progression and inclusion criteria for clinical trials. Our previous work has shown that medical comorbities such as dyslipidemia, diabetes, kidney disease and hypertension can impact the levels of these biomarkers and there are ethnic differences in this relationship. The current study extended this work by investigating the effect of inflammation on levels of plasma biomarkers of amyloid, tau and neurodegeneration in an ethnically diverse cohort.MethodData from 651 cognitively unimpaired non‐Hispanic White and 646 cognitively unimpaired Mexican American participants from the Health & Aging Brain Study‐ Health Disparities study were analyzed. Plasma markers of Aβ40, Aβ42, total tau and NfL were assayed using the ultrasensitive Simoa (single‐molecule array) technology. The relationship of peripheral inflammatory biomarkers (IL‐6, IL‐10, TNFα & CRP) to each of the AD plasma biomarkers was analyzed using partial correlation controlling for age, sex and APOE4 positivity.ResultHigher levels of Aβ40, Aβ42, total tau and NfL were associated with elevated IL‐6, IL‐10 and TNFα for both ethnic groups. CRP was not significantly associated with any of the AD biomarkers for either group. Although the Mexican American participants had significantly lower Aβ40 (p = .000) and higher total tau (p = .000) than non‐Hispanic White participants, the two groups did not differ significantly on the level of any of the inflammatory markers.ConclusionThe level of plasma AD biomarkers is influenced by the presence of peripheral inflammatory cytokines. CRP a non‐specific acute phase marker of inflammation is not related to plasma AD biomarkers in cognitively unimpaired older adults. Ethnicity in this bi‐ethnic study was not a factor in this relationship. Additional research investigating medical co‐morbidities as a factor in the inflammation‐AD plasma biomarker relationship is needed. As with medical co‐morbidities the level of inflammation may affect the interpretation and application of the plasma AD biomarkers in this study.