Plasma glial fibrillary acidic protein is an early and specific marker of amyloid‐β pathology in Alzheimer's disease. (31st December 2021)

• Record Type: Journal Article
• Authors: Pereira, Joana B.; Janelidze, Shorena; Smith, Ruben; Mattsson‐Carlgren, Niklas; Palmqvist, Sebastian; Zetterberg, Henrik; Stomrud, Erik; Ashton, Nicholas J.; Blennow, Kaj; Hansson, Oskar
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 5
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-31
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.055538
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Glial fibrillary acidic protein (GFAP) is a marker of astrogliosis, which is often observed surrounding amyloid‐β (Aβ) plaques in the brains of patients with Alzheimer's disease (AD). GFAP can be measured both in plasma and cerebrospinal fluid (CSF). The aim of this study was to assess whether plasma and CSF GFAP are independently related to Aβ or tau burden in cognitively unimpaired (CU) and cognitively impaired (CI) individuals. Method: We measured plasma GFAP and CSF GFAP using the Single molecule array (Simoa) and NeuroToolKit robust prototype assays (Roche Diagnostics) in a sample of 217 CU individuals without Aβ pathology, 71 CU individuals with Aβ pathology, as well as 78 CI subjects with Aβ pathology from the Swedish BioFINDER‐2 cohort. Aβ pathology was defined using CSF Aβ42/40 with a cutoff of < 0.752 determined using mixture modeling. All subjects underwent Aβ ( 18 F‐flutemetamol) and tau ( 18 F‐RO948) positron emission tomography (PET). Differences between groups in GFAP markers were assessed using an analysis of covariance, adjusting for age and sex. Linear regression analyses were performed within each group to assess the relationship between GFAP markers with neocortical Aβ‐PET and temporal tau‐PET. Result: Plasma GFAP was significantly elevated in all Aβ‐positive groups compared to subjects without Aβ pathology (p<0.01). In addition, this marker was associated with higher Aβ‐PET burden in CU individuals (p<0.001), even in the subgroup with normal CSF Aβ42/40 values (p=0.022). Plasma GFAP was also associated with Aβ‐PET in the CI group (p<0.001). All of these associations remained significant after controlling for tau‐PET burden. Further, plasma GFAP could predict Aβ‐PET outcome in the CU and CI groups with an area under the curve of 71%. In contrast, although correlations were also observed between tau‐PET and GFAP, these were no longer significant after controlling for Aβ‐PET. CSF GFAP did not show any differences between groups and correlated with Aβ‐PET only in CI individuals (p=0.005). Conclusion: These findings suggest that plasma GFAP is an early and specific marker associated with brain Aβ but not tau aggregation, even in cognitively normal individuals with normal CSF Aβ42/40.