Comparison between plasma, serum and cerebrospinal fluid glial fibrillary acidic protein in Alzheimer’s Disease and Dementia with Lewy bodies and the effect of age and sex on diagnostic performance

Abstract

BackgroundGlial fibrillary acidic protein (GFAP) is a novel Alzheimer’s Disease (AD) biomarker that associates with amyloid pathology and pathology‐related changes can be detected in different biofluids. We studied how the performance of GFAP to distinguish between controls, AD and dementia with Lewy bodies (DLB), depends on the studied biofluid (cerebrospinal fluid (CSF), serum or plasma) and the confounding effects of age or sex.MethodFrom the Amsterdam Dementia Cohort and a local repository of healthy controls we included 372 cognitively normal individuals (CN), 255 patients with AD and 120 patients with DLB (Table 1) and GFAP levels were measured in one (n=322), two (n=416) or three (n=9) biofluids. GFAP was measured using Simoa in CSF (n=473), plasma (n=257) and serum (n=451) samples. For individuals with DLB, GFAP was measured in CSF and serum only. Effects of clinical diagnosis, age and sex on GFAP levels in each body fluid were estimated with linear models. Estimated differences between diagnostic groups were corrected for age and sex, age effects were corrected for sex and diagnostic group, and sex effects were corrected for age and diagnostic group.ResultGFAP levels were increased in AD relative to controls in all biofluids (fold change (FC): 1.6(CSF), 1.9(plasma) and 1.4(serum), p‐values<0.001) and increased in AD relative to DLB (FC: 1.7(CSF) and 1.3(serum), p‐values<0.001, Figure 1). No difference was found between DLB and controls. CSF GFAP levels increased with age in all clinical groups (range of standard deviation protein level increase per year (SD/year): 0.020‐0.024), while plasma GFAP levels increased with age only in CN (SD/year: 0.032). Serum GFAP levels increased with age in CN and DLB (SD/year: 0.058(CN) and 0.074(DLB), Figure 2). CSF GFAP showed sex effects in AD only (FC in males compared to females: 1.1), whereas serum GFAP showed sex effects in all clinical groups (FC in males: 0.83(AD), 0.85(NC) and 0.72(DLB)), and plasma GFAP showed no sex effects (Figure 3A‐C).ConclusionDifferences in GFAP levels between clinical diagnoses showed the same trend for all three matrices. With older age, differences in GFAP levels between controls and AD become harder to detect.