P0011 - Appearance of macromolecular form of Fibronectin in dementia patients

Abstract

Background:

Fibronectin(FN) is a multidomain adhesive glycoprotein present in connective tissue on cell surfaces in insoluble fibrilar form.

Objective:

Because of reported experimental evidences for a very large elasticity of the FN molecule and in view of the hypothesis that conformational changes precede its function, we were interested in analyzing: 1)the eventual appearance of macromolecular form of fibronectin, 2) the expressions of the cellular, collagen, fibrin, and C-terminal fibronectin domains in the blood plasma of Alzheimer's(14 patients, mean age 70.2+/-6.5), vascular dementia patients(24 patients, mean age 73.1+/-5.3), and age-matched control(30 subjects, mean age 73.4+/-7.4).

Methods:

The fibronectin domain concentrations were determined by ELISA using panel of domain-specific monoclonal antibodies. Western immunoblotting by the use a monoclonal antibody was performed to analyze the FN molecular forms.

Results:

Immunoblotting pattern of plasma fibronectin of both dementia groups and age-matched group consisted of two FN bands(220-230 kDa), and some of them showed additionally of 2-3 macromolecular bands having molecular masses 260 and 350 kDa. However, the appearance of macromolecular fibronectin forms(260 and 350 kDa) happened more frequently in Alzheimer's dementia(85% of samples)than in samples with vascular dementia(50%) as well as in age-matched control(53%).Among the analysed domain expression on fibronectin, only the concentration of the C-terminal fibronectin domain(747.1+/-79 ug/ml)was significantly higher(p<0.004)than that in age-matched control group(635.7+/-120ug/ml, whereas its level was negligible different in vascular dementia(659.2+/-137ug/ml).

Conclusions:

The occurence of macromolecular forms of fibronectin seems to be associated more frequently with Alzheimer's dementia. Increased concentration of C-terminal domain suggests some conformational alterations of fibronectin present in Alzheimer's samples.