Gene expression as peripheral biomarkers for sporadic Alzheimer's disease.

Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. We investigated the profiles of 33 genes, previously found by our group to have altered expression in postmortem brains of AD. The gene profiles were studied via quantitative-real-time-reverse-transcription-polymerase-chain-reaction, in whole blood samples (collected with the PAXgene blood RNA system) isolated from a population clinically diagnosed with AD and healthy controls (1-year period/ up to 4 samples). Five genes showed significant correlation to the dementia score, Mini-Mental State Examination (MMSE). Focusing on the two genes with the smallest p-value, H3-histone and cannabinoid-receptor-2, notable increases in these genes were found in peripheral blood mRNA in subjects with lower MMSE scores. Seasonal variations in gene expression were not significant due to sample size, but did seem to vary due to time of sample withdrawal. In conclusion, gene expression profiling might be a promising method to investigating a large population with the aim of developing an early diagnosis of AD.

Auricular vagus somatosensory evoked potentials in vascular dementia.

A new method for the assessment of vagus nerve function has recently been introduced into clinical practice. In the present study we could show that, contrary to our results in Alzheimer's disease (AD), in patients with vascular dementia (VaD) vagus sensory evoked potentials (VSEP) did not show statistically significant differences as compared to healthy controls. Thus, we hypothesize that the new method of VSEP could possibly contribute to a differential diagnosis between early cases of AD and VaD.

Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters.

The method of vagus somatosensory evoked potentials (VSEP) was introduced to easily measure the activity of vagus brain stem nuclei. In Alzheimer's disease, this measure was characterized by longer latencies as compared to controls while amplitudes did not show statistical significant differences at frontal and central recording sites. Therefore, the influence of stimulation and recording parameters on amplitudes of VSEP were systematically examined. In 20 healthy participants, VSEP measurement was done by electrical stimulation of the cutaneous representation of the vagus nerve in the external auditory channel and recording of VSEP over the scalp. The optimum stimulation intensity is 8 mA without perception of pain. There is no effect of stimulation side or gender. Maximum VSEP amplitudes are detected at bipolar recordings comprising the electrode T4 without statistically significant differences of latencies, wave shape and polarity. Thus, recordings of future examinations should be performed at 8 mA including this temporal electrode position. The reason for focussing on brain stem evoked potentials is that recent work has accumulated evidence for this area being involved in early phases of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Improved methodological knowledge may facilitate the assessment of this non-invasive and cost-effective method in the early diagnosis of neurodegenerative disorders.

Age effect on far field potentials from the brain stem after transcutaneous vagus nerve stimulation.

Recently, a new electrophysiological method for the assessment of vagus nerve function in the brainstem has been proposed in healthy participants. Before this procedure may be applied to patients with neurodegenerative diseases, its feasibility in elderly healthy participants and a possible age effect on the measurement have to be investigated. The vagus sensory evoked potentials (VSEP) after transcutaneous electric stimulation of the sensory auricular branch of the vagus nerve have been assessed in healthy younger and elderly participants. VSEP measured as far field potentials probably originating in vagus nuclei in the brainstem were recorded in 20 of 22 younger as well as in 39 of 43 elderly healthy participants. Latencies were significantly longer in the elderly as compared to the younger participants, while no clear age effects on amplitudes were identified. These results indicate that the assessment of VSEP is feasible also in elderly healthy participants. This is a prerequisite for testing this method in elderly patients with neurodegenerative diseases like Alzheimer and Parkinson disease as a noninvasive tool to detect an affection of the brainstem nuclei of the vagus nerve early in their course.

Sensory gating deficit in a subtype of chronic schizophrenic patients.

The dual click P50 paradigm has been established as a neurophysiological method to detect gating mechanisms. Studies of schizophrenic patients have shown that an insufficient reduction of the P50 amplitude after the second relative to the first stimulus indicates a deficient sensory gating mechanism. The aim of this study was to compare the P50 responses in the dual click paradigm of healthy volunteers to those of patients with different psychotic disorders, especially with regard to psychopathology and nosology according to ICD-10 and DSM-IV and to the classification system of Leonhard. A total of 34 patients and 12 healthy volunteers were investigated electrophysiologically while they performed the P50 dual click experiment. Patients with prominent negative symptoms and without perceptual abnormalities and patients with a hebephrenic subtype of schizophrenia showed less suppression in the dual click P50 paradigm than did healthy controls. Patients with brief/acute and transient psychotic disorders or cycloid psychoses did not differ from healthy volunteers with regard to suppression in the dual click P50 paradigm. No striking influence of gender, age, duration of disease and present medication was found. The findings confirm the lack of sensory gating measured by the dual click P50 paradigms in some but not all patients with schizophrenia. Both subtype of schizophrenia and current form of psychopathology appear to be related to the presence or absence of abnormal sensory gating.