Glial Cell-Line Derived Neurotrophic Factor (GDNF) Concentrations in Cerebrospinal Fluid and Serum of Patients with Early Alzheimer's Disease and Normal Controls

Issue title: Mini-Forum: Roles of Amyloid-β and Tau Phosphorylation in Neuronal Repair and Protection

Guest editors: Garth Bissette

Article type: Research Article

Authors: Straten, Guido^{a; b} | Eschweiler, Gerhard W.^{a; b} | Maetzler, Walter^c | Laske, Christoph^a | Leyhe, Thomas^{a; b; *}

Affiliations: [a] Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany | [b] Geriatric Center at the University Hospital of Tübingen, Tübingen, Germany | [c] Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany | Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA

Correspondence: [*] Corresponding author: Dr. Thomas Leyhe, University of Tübingen, Department of Psychiatry and Psychotherapy, Osianderstraße 24, 72076 Tübingen, Germany. Tel.: +49 7071 2982311; Fax: +49 7071 294141; E-mail: thomas.leyhe@med.uni-tuebingen.de.

Abstract: As neurotrophic factors play an important role in development and maintenance of global central nervous system (CNS) function, we supposed that glial cell-line derived neurotrophic factor (GDNF), which has been extensively studied for its survival promoting effects especially concerning catecholaminergic neurons, also plays a significant role in neurodegenerative disease characterized mainly by damage of cholinergic CNS neurons like AD. Here we compared GDNF concentrations in serum and cerebrospinal fluid (CSF) of patients with probable Alzheimer's disease (AD) and normal controls (NC). While GDNF concentrations in CSF were significantly increased in patients with AD (291.7 ± 85.8 pg/ml) compared with NC subjects (218.7 ± 93.3 pg/ml, p = 0.012), GDNF concentration of AD patients (486.5 ± 72.3 pg/ml) in serum were significantly decreased compared with the NC group (711.5 ± 186.5 pg/ml, p < 0.001). Increased GDNF in CSF of AD might be due to an upregulated expression in CNS as an adaptive process of the impaired brain to enhance neurotrophic support at least in early stages of disease and/or impairment of CSF turnover. Decreased serum concentration of GDNF might be related to altered function of the blood brain barrier thus disturbing clearance or facilitating passover of potentially harmful metabolites.

Keywords: Alzheimer's disease, blood brain barrier, glial cell-line derived neurotrophic factor (GDNF), neuroprotection, neurotrophic effect

DOI: 10.3233/JAD-2009-1146

Journal: Journal of Alzheimer's Disease, vol. 18, no. 2, pp. 331-337, 2009