Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

Abstract

Background: Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects.

Methods: We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia.

Results: We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group.

Conclusion: These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD.

Figure 1

Comparison of the 2-DE gels loaded with CSF from a AD patient. All gels were loaded with 50 μg CSF proteins and the second dimension of separation, polyacrylamide gel electrophoresis, was then performed using 12 %T acrylamide slab gels. 2-DE gels were silver stained to visualize all proteins.

Figure 2

Two-dimensional gel electrophoresis gel image using a CSF sample from an AD patient. Spots that were found to particularly expressed spots are arrow marked. These spots identified by fibrinogen gamma-A chain precursor. The identified spots had a molecular weight of about 50 kDa and a pI of 5.6.

Figure 3

Differentially expressed spots of fibrinogen gamma-A chain precursor. Shown (arrow marked) is the increase in expression pattern according to progression of disease. The findings were confirmed on a repeat experiment.