C.E. Teunissen

Inflammation markers in relation to cognition in a healthy aging population.

The relation between serum inflammatory protein levels and cognitive performance was investigated in a healthy population. Individuals were tested during 6 years of follow-up. Serum concentrations of 10 inflammatory proteins were correlated to cognitive speed (Letter-Digit Coding Test, LDCT), attention and information processing (Stroop) and memory (Word Learning). Haptoglobin levels at baseline correlated negatively with cognitive performance on the Stroop and Word Learning Recall test over the 6 years follow-up period. C-reactive protein (CRP) levels at baseline correlated negatively with performance on the Word Learning tests over the 6 years follow-up period. Thus, relatively high concentrations of haptoglobin and C-reactive protein may be indicative for impaired cognitive performance.

Combination of serum markers related to several mechanisms in Alzheimer’s disease

Alzheimers disease (AD) probably involves several pathobiochemical mechanisms and this may be reflected by changes in different serum components. The present study investigated whether the combined analysis of serum molecules related to different mechanisms improves the discrimination of AD patients from healthy controls. Serum of patients with AD was analyzed for a broad spectrum of marker molecules, including 11 inflammatory proteins, 12 sterol intermediates and phytosterols, 2 brain-specific proteins and 4 constituents involved in homocysteine homeostasis. The serum molecule concentrations were combined in a logistic regression model, using a forward stepwise inclusion mode. The results showed that the combination of interleukin-6 (IL-6) receptor, protein alpha1 fraction, cysteine and cholesterol concentrations improved the discrimination between AD patients and healthy controls compared to the single markers. In conclusion, the results of this study have shown that the complex pathology in AD is reflected in a pattern of altered serum concentrations of several marker molecules related to several pathobiochemical mechanisms.

Serum cholesterol, precursors and metabolites and cognitive performance in an aging population

The present study investigated if a causal relation exists between serum concentrations of precursors and metabolites of cholesterol and cognitive performance in a healthy aging population. Cognitive function addressing four domains of 144 individuals (30-80 years) was tested at baseline and after 6 years of follow-up. Serum concentrations of different sterols related to cholesterol were measured. Serum levels of lathosterol and lanosterol correlated negatively with cognitive performance on the Word Learning tests for verbal learning and memory. This was observed at baseline and follow-up and was independent of age, sex and educational level. Furthermore, the levels of lathosterol and lanosterol at baseline correlated with performance on the Stroop test and Word Learning tests over the 6-year follow-up period. Serum levels of 27-hydroxycholesterol and 24S-hydroxycholesterol showed inconsistent correlations, while cholesterol, desmosterol, sitosterol and campesterol were not related to cognitive performance.Thus, relative high serum ratios of the cholesterol precursors lanosterol and lathosterol, indicative for a high rate of endogenous cholesterol synthesis, are associated with relatively low memory performance in this aging population.

Behavioural correlates of striatal glial fibrillary acidic protein in the 3-nitropropionic acid rat model: disturbed walking pattern and spatial orientation.

The 3-nitropropionic acid animal model is a model where excitotoxicity, mitochondrial dysfunction and oxidative stress, mechanisms common to various neurodegenerative diseases, are involved. The present study investigated whether behavioural alterations in this model were related to striatal damage. Wistar and Lewis rats were exposed to 3-nitropropionic acid and their behavioural performance (open field, walking pattern and Morris Water Maze task) was tested after the injections and after a recovery period of 3 weeks. No changes in activity were found in the open field test. Altered walking pattern was observed in the footprint analysis, although a different response was observed in the Wistar rats compared to the Lewis rats. Initially increased latency times were observed during visual discrimination learning in the Morris Water Maze task in 3-nitropropionic acid-treated Wistar rats compared to Wistar controls. During spatial discrimination learning (invisible platform) in the Morris Water Maze task the swimming velocity was decreased in both rat strains as a result of 3-nitropropionic acid treatment. Increased striatal glial fibrillary acidic protein concentration in Wistar rats correlated with several parameters of the footprint analysis and with the latency and distance in visual as well as spatial discrimination learning in the Morris Water Maze. It is concluded that measurement of walking pattern and spatial orientation performance are sensitive indicators to monitor behavioural changes in relation to striatal degeneration in the 3-nitropropionic acid animal model. In addition, Lewis rats are less sensitive towards 3-nitropropionic acid treatment than Wistar rats.

Presence of soluble and particulate guanylyl cyclase in the same hippocampal astrocytes

The localisation of particulate and soluble guanylyl cyclase was studied in hippocampal astrocytes. Counting the colocalisation of cGMP immunoreactivity with the astrocytic marker glial fibrillary acidic protein after stimulation of brain slices with sodium nitroprusside (0.1 mM) or atrial natriuretic peptide (100 nM), we were able to show that at least 67% of the hippocampal astrocytes contained both guanylyl cyclase isoforms. In addition, it was shown that a large number of atrial natriuretic peptide, brain-derived natriuretic peptide or sodium nitroprusside responsive cells contain the beta1-subunit of the soluble guanylyl cyclase. The results show that, in at least a subset of hippocampal astrocytes, soluble and particulate guanylyl cyclases are simultaneously present in the same cells.

Concentrations of Different Sterols in the Striatum and Serum of 3-Nitropropionic Acid-Treated Wistar and Lewis Rats

In the present study, we examined the long-term effect of oxidative stress induced neurodegeneration on sterol concentrations in striatum and serum of Wistar and Lewis rats. Three weeks after treatment with 3-nitropropionic acid, no differences in 24S-hydroxycholesterol concentrations were observed in striatal homogenates and serum. Ratios of striatal campesterol to cholesterol were higher after 3-nitropropionic acid treatment as compared to controls of both rat strains suggesting an increased passage of this exogenous plant sterol across the blood-brain-barrier. Ratios of lathosterol to cholesterol in serum and striatum were lower in treated rats as compared with controls of both rat strains. Absolute concentrations of serum and striatal cholesterol precursors and plant sterols differed between the controls of both rat strains. It was concluded that the changes observed in sterol concentrations in the striatum and serum indicate that cholesterol homeostasis may be affected during neurodegenerative processes associated with blood-brain-barrier damage.