Abstract

Alzheimer’s disease (AD) and normal pressure hydrocephalus (NPH) are common forms of dementia in the elderly. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain.

BDNF serum and cerebrospinal fluid (CSF) concentrations were assessed by a sensitive ELISA in 27 AD patients in comparison to 9 NPH patients and 28 age-matched healthy controls (10 CSF samples).

We found a significant decrease of BDNF serum concentration in AD (18.6 ng/ml) and NPH patients (18.1 ng/ml) as compared to healthy controls (21.3 ng/ml; p = 0.041/p = 0.017). BDNF serum concentrations did not correlate with CSF levels, age or MMSE scores both in AD and NPH patients. In unconcentrated CSF samples, BDNF could be detected in AD patients in 8/27 cases (29.6%; mean of 4.6 pg/ml), in NPH patients in 1/9 cases (11.1%; mean of 6.4 pg/ml) and in the control subjects in 5/10 cases (50%; mean of 1.6 pg/ml) with no significant differences as regards mean concentration and frequency of detectable BDNF in CSF.

The decrease of BDNF serum levels in AD and NPH may reflect a lack of trophic support and thus contribute to progressive degeneration in both diseases. In contrast to serum, CSF seems to be no useful source to determine BDNF in AD or NPH because of too low concentrations. Further examinations have to follow to elucidate the potential sources and the meaning of reduced BDNF levels in the blood in AD and NPH.

Keywords: Brain-derived neurotrophic factor; Serum; CSF; Alzheimer’s disease; Normal pressure hydrocephalus; Healthy controls; MMSE

Article Outline

1. Introduction

2. Materials and methods

2.1. Subjects and clinical assessment

2.2. Measurement of BDNF concentrations in serum

2.3. Measurement of BDNF concentrations in CSF

2.4. Statistical analysis

3. Results

3.1. In vivo concentrations of BDNF in serum

3.2. Influence of MMS on BDNF serum concentrations

3.3. Influence of age on BDNF serum concentrations

3.4. In vivo concentrations of BDNF in CSF

3.5. Comparisons between BDNF levels in serum and CSF

3.6. Comparisons between AD patients with BDNF+ and BDNF− CSF

4. Discussion

4.1. Decreased BDNF serum concentration in AD and NPH and possible underlying mechanisms

4.2. Potential sources of BDNF in serum and plasma

4.3. No influence of age on BDNF serum concentration

4.3.1. BDNF in CSF in AD and NPH

4.3.2. BDNF in CSF in other neurological diseases

4.3.3. Potential neuroprotective effects of BDNF in AD

4.3.4. BDNF as a treatment target for Alzheimer’s disease

5. Conclusions

References