Plasma biomarkers of Alzheimer’s Disease associate with gray matter volume and cerebral glucose metabolism in older adults with Mild Cognitive Impairment

Abstract

AbstractBackgroundAlzheimer’s Disease (AD) pathology in vivo has traditionally been measured in the cerebrospinal fluid or by positron emission tomography (PET). Developments in measuring plasma biomarkers present less invasive, cheaper ways to quantify AD pathology. However, the associations between these new plasma markers and neuroimaging markers of AD are not fully understood. We examined the relationship between plasma biomarkers of AD and measures of whole brain gray matter volume (GMV) and cerebral glucose metabolism in both cognitively unimpaired (n = 83) and impaired (n = 30) individuals.MethodWe collected data from individuals within the University of Kansas Alzheimer’s Disease Research Center’s (KU ADRC) Clinical Cohort who underwent MRI and FDG‐PET scans and had available plasma data. Participants included 64 females, and age of the neuroimaging cohort was 76.0 ± 6. Plasma biomarkers were measured in EDTA plasma using the Quanterix Simoa® HD‐X, and included NfL, Aβ42, Aβ40, GFAP, and p‐tau181. GMV was estimated using MPRAGE MRI processed in FreeSurfer. Cerebral glucose metabolism was estimated from FDG‐PET data using SUVR values calculated through SPM12, with standardization to pons. We used linear regression to examine the relationship between each biomarker to whole brain GMV and glucose metabolism. ANCOVA was used to evaluate differences in the plasma biomarkers between diagnosis groups. Analyses included sex and age as covariates.ResultWhole brain GMV (F = 8.4, p = .004) and cerebral glucose metabolism (F = 10.9, p = .002) differed between diagnostic groups. In the linear regression, we observed an interaction effect between cognitive diagnosis and each biomarker, such that the slopes of regressions between each plasma biomarker and neuroimaging marker was significant in the impaired group, but not significant in the unimpaired. In the impaired group, the strongest association observed was between plasma NFL and whole brain GMV (β = ‐1.4, p = .020) and cerebral glucose metabolism (β = ‐1.7, p = .014). Additionally, all plasma biomarkers were found to differ between diagnostic groups.ConclusionWe show that plasma markers of AD pathology associate with whole brain GMV and cerebral glucose metabolism in individuals with cognitive impairment. Further work will examine the relationship between biomarkers and regional neuroimaging measures