Volume 3, Issue 8 p. 1476-1485
Research Article

Analysis of gial acidic fibrillary protein in the human entorhinal cortex during aging and in Alzheimer's disease

Raymonde Porchet

Raymonde Porchet

Institut de Biologie Cellulaire et de Morphologie, Lausanne, Switzerland

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Alphonse Probst

Alphonse Probst

Institute of Pathology, University Hospital Basel, Switzerland

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Constantin Bouras

Constantin Bouras

Department of Psychiatry, University of Geneva School of Medicine, Geneva, Switzerland

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Eduarda Dráberová

Eduarda Dráberová

Institute of Molecular Genetics, Academy of Sciences, Prague, Czech Republic

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Pavel Dráber

Pavel Dráber

Institute of Molecular Genetics, Academy of Sciences, Prague, Czech Republic

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Beat M. Riederer

Corresponding Author

Beat M. Riederer

Institut de Biologie Cellulaire et de Morphologie, Lausanne, Switzerland

Centre des Neurosciences Psychiatriques, Hôpital Psychiatrique, Prilly, Switzerland

Institut de Biologie Cellulaire et de Morphologie, Rue du Bugnon 9, 1005 Lausanne, Switzerland Fax: +41-21-692-5105===Search for more papers by this author
First published: 12 August 2003
Citations: 81

Abstract

Glial fibrillary acidic protein, GFAP, is a major intermediate filament protein of glial cells and major cytoskeletal structure in astrocytes. The entorhinal cortex has a key role in memory function and is one of the first brain areas to reveal hallmark structures of Alzheimer's disease and therefore provides an ideal tissue to investigate incipient neurodegenerative changes. Here we have analyzed age- and disease-related occurrence and composition of GFAP in the human entorhinal cortex by using one- and two-dimensional electrophoresis, Western blots and immunocytochemistry combined with confocal microscopy. A novel monoclonal antibody, GF-02, was characterized that mainly reacted with intact GFAP molecules and indicated that more acidic and soluble GFAP forms were also more susceptible to degradation. GFAP and vimentin increased with aging and in Alzheimer's disease (AD). Two-dimensional electrophoresis and Western blots revealed a complex GFAP pattern, both in aging and AD with different modification and degradation forms. Immunohistochemistry indicated that reactive astrocytes mainly accumulated in relation to neurofibrillary tangles and senile plaques in deeper entorhinal cortex layers. GFAP may be used as an additional but not exclusive diagnostic tool in the evaluation of neurodegenerative diseases because its levels change with age and respond to senile plaque and tangle formation.