Glial fibrillar acidic protein in the cerebrospinal fluid of Alzheimer's disease, dementia with Lewy bodies, and frontotemporal lobar degeneration

Abstract

Biomarkers in the cerebrospinal fluid (CSF) are currently regarded as indispensable indicators for accurate differential diagnosis of neurodegenerative disorders. Although high levels of astrocyte-secreted glial fibrillar acidic protein (GFAP) in the CSF of patients with Alzheimer's disease (AD) have been reported, the levels of GFAP in the CSF have not been fully investigated in other neurological disorders that cause dementia, such as dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). In this study, we determined the levels of GFAP in the CSF of healthy control subjects and AD, DLB, and FTLD patients to address two questions: (i) Do the levels of GFAP differ among these disorders? and (ii) Can GFAP be used as a biomarker for the differential diagnosis of these neurodegenerative disorders? The levels of GFAP in AD, DLB, and FTLD patients were significantly higher than those in the healthy control subjects. Although the levels of GFAP were not significantly different between AD and DLB patients, a higher level of GFAP was observed in FTLD patients than in AD and DLB patients. It is concluded that representative neurological disorders causing dementia were associated with higher levels of GFAP in the CSF.

Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase

“…Our results support previous observations of increased YKL-4023 24 and GFAP28 in CSF of patients with sFTD and we could demonstrate similar changes in gFTD. Thus, our data indicate a similar neuroinflammatory profile in gFTD and sFTD and support the notion that it is a shared mechanism in gFTD and sFTD pathophysiology.…”

Quantitative Proteomic Profiling of Cerebrospinal Fluid to Identify Candidate Biomarkers for Alzheimer's Disease

“…Glial fibrillary acidic protein (GFAP) is also known as a marker of astrocytosis in neurodegeneration associated with neurological disorders. Higher levels of GFAP in CSF have been reported in neurodegenerative disorders including AD, dementia with Lewy bodies (DLB), and frontotemporal dementia (FTLD) [18]. GFAP levels in CSF are also elevated in Creutzfeldt-Jakob disease (sCJD) patients [29].…”

“…Based on the current literature, this is the largest quantitative CSF proteome for Alzheimer’s disease reported thus far. Among the proteins that were differentially expressed in patients with AD were neuronal cell adhesion molecule-1 [16, 17], glial fibrillary acidic protein [18], microtubule associated protein Tau [18], neuronal pentraxin 2 [19], VGF nerve growth factor inducible (VGF)[20] and secretogranin II (SCG2)[20], which have already been reported by other groups to be altered in the CSF of AD dementia patients thereby validating the feasibility of our approach. Multiplexed parallel reaction monitoring (PRM) assays developed to quantitate a subset of these candidate biomarkers in CSF confirmed the alterations that were observed in the discovery experiments.…”

Delirium and Alzheimer disease: A proposed model for shared pathophysiology

“…CSF concentration of GFAP has been shown to be elevated in AD, as well as in other neurodegenerative dementias 38 though other studies found no difference between AD and controls or between AD and other neurodegenerative conditions 39 . GFAP has not been demonstrated to be increased in delirium 40 .…”