Transgenic tomatoes expressing human beta-amyloid for use as a vaccine against Alzheimer’s disease

Human β-amyloid (Aβ) is believed to be one of the main components of Alzheimer’s disease, so reduction of Aβ is considered a key therapeutic target. Using Agrobacterium-mediated nuclear transformation, we generated transgenic tomatoes for Aβ with tandem repeats. Integration of the human Aβ gene into the tomato genome and its transcription were detected by PCR and Northern blot, respectively. Expression of the Aβ protein was confirmed by western blot and ELISA, and then the transgenic tomato line expressing the highest protein level was selected for vaccination. Mice immunized orally with total soluble extracts from the transgenic tomato plants elicited an immune response after receiving a booster. The results indicate that tomato plants may provide a useful system for the production of human Aβ antigen

NeuroGrid: recording action potentials from the surface of the brain.

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders

Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study

Doc number: 72 Abstract Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model. Methods/design: In a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered. Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period. A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers. Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems. Trial registration: NCT0145089

Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers

Background: Drug addiction is associated with significant disease and death, but its impact on the ageing process has not been considered. The recent demonstration that many of the items available in routine clinical pathology have applicability as biomarkers of the ageing process implies that routine clinical laboratory parameters would be useful as an initial investigation of this possibility. Methods: 12,093 clinical laboratory results 1995-2006 were reviewed. To make the age ranges of the medical and addicted groups comparable the age range was restricted to 15-45 years. Results: 739 drug addicted (DA) and 5834 general medical (GM) age matched blood samples were compared. Significant elevation of immune parameters was noted in the C-reactive protein, erythrocyte sedimentation rate, total lymphocyte count, serum globulins and the globulin:albumin ratio (P < 0.01). Alanine aminotranferase, creatinine, urea, and insulin like growth factor-1 were also significantly higher (P < 0.01) in the DA group. Albumin, body mass index and dihydroepiandrosterone sulphate were unchanged and cholesterol was lower (all P < 0.05). Conclusion: These data demonstrate for the first time that addiction is associated with an altered profile of common biomarkers of ageing raising the possibility that the ageing process may be altered in this group. Infective and immune processes may be centrally involved. They suggest that addiction forms an interesting model to further examine the contribution of immune suppression and hyperstimulation to the ageing process

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p