High plasma Glial Fibrillary Acidic Protein levels are associated with an increased risk of dementia and Alzheimer’s disease over a 13‐year follow‐up period: Results from a prospective population‐based cohort

Abstract

AbstractBackgroundReactive astrogliosis, an activation state that includes morphological, metabolic and functional changes of astrocytes, occurs in neurodegenerative diseases, including Alzheimer’s disease (AD). Increased plasma levels of glial fibrillary acidic protein (GFAP), a reactive astrogliosis biomarker, have been recently reported in the preclinical and symptomatic stages of AD. However, very few works have investigated its ability to predict long‐term AD risk. This study aimed to investigate the association between plasma GFAP levels and future risk of dementia and AD.MethodWithin the Bordeaux‐3C prospective population‐based cohort, we quantified plasma GFAP levels using V‐PLEX immunoassay among 1068 non‐demented participants aged 69 years or over. Dementia was screened over a follow‐up of 13 years. Associations of baseline plasma GFAP levels with the risk of incident AD and dementia were investigated using Cox models adjusted for socio‐demographic characteristics, cardio‐vascular comorbidities and APOE4 status.ResultThe mean age of the participants was 77.6 years (std 4.7) and 64% were women. Median GFAP level was 239 pg/ml [IQR 192‐321]. During the follow‐up (median 8.8 years, up to 14.3 years), 281 dementias occurred, including 120 probable AD. In multivariate models, the middle and high tertiles of GFAP were associated with an increased risk of dementia (aHR = 1.8, 95%CI: 1.3 to 2.5 and aHR = 2.0, 95%CI: 1.5 to 2.8 respectively, compared to the lower tertile, global p‐value<.0001). These risks were higher when considering only probable AD (aHR = 2.7, 95%CI: 1.5 to 4.7 and aHR = 3.0, 95%CI: 1.7 to 5.2 for the middle and high tertiles respectively, global p‐value 0.0004). The association was found regardless of the APOE4 status. There was no interaction with time meaning that baseline GFAP was associated with higher risk of AD at short as at long‐term.ConclusionThese results suggest that plasma GFAP levels are increased very early in the process of AD. GFAP could represent a useful means to identify people at high risk of AD for both an objective of prevention or to include them in clinical trials. The interest of such a marker, alone or in combination with other plasmatic biomarkers of AD, should be further studied.