Alina Andras

Alpha-and Gamma-Synuclein Proteins Are Present in Cerebrospinal Fluid and Are Increased in Aged Subjects with Neurodegenerative and Vascular Changes

Background: Disease-specific biomarkers should reflect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases. Several synaptic proteins have been described in cerebrospinal fluid (CSF) of patients with dementia. In Lewy body disease α-synuclein is incorporated within Lewy bodies and α-, β- and γ-synucleins in dystrophic neuritis. These pathological changes are expected to be seen in CSF. Methods: A total of 25 CSF post-mortem samples (8 control and 17 subjects with dementia) were used to quantify α- and γ-synucleins and IgG. Results: We describe for the first time the presence of γ-synuclein in CSF. There is an elevation of both α- and γ-synucleins in CSF from elderly individuals with Alzheimer’s disease, Lewy body disease (LBD) and vascular dementia (CVD), compared to normal controls. γ-Synuclein showed a greater elevation in LBD, IgG in CVD. The elevation of α- and γ-synucleins was seen from Braak stage III onwards and remained stable until Braak stage VI. These results were not influenced by age at death or post-mortem delay. Conclusions: The reported increases in α- and γ-synucleins and IgG in the ventricular CSF of individuals with dementia are novel findings. They now need to be explored further using a greater number of cases in each subgroup, using lumbar CSF samples to determine their applicability and relevance to a clinical diagnostic setting. It needs to be established whether using these markers may help to discriminate LBD from other types of neurodegenerative and vascular dementias.

Synaptic Proteins and Choline Acetyltransferase Loss in Visual Cortex in Dementia With Lewy Bodies

Abstract Functional neuroimaging studies have consistently reported abnormalities in the visual cortex in patients with dementia with Lewy bodies (DLB), but their neuropathologic substrates are poorly understood. We analyzed synaptic proteins and choline acetyltransferase (ChAT) in the primary (BA17) and association (BAs18/19) visual cortex in DLB and similar aged control and Alzheimer disease (AD) subjects. We found lower levels of synaptophysin, syntaxin, SNAP-25, and &ggr;-synuclein in DLB subjects versus both aged control (68%–78% and 27%–72% for BA17 and BAs18/19, respectively) and AD cases (54%–67% and 10%–56% for BA17 and BAs18/19, respectively). The loss in ChAT activity in DLB cases was also greater in BA17 (72% and 87% vs AD and control values, respectively) than in BAs18/19 (52% and 65% vs AD and control groups, respectively). The observed synaptic and ChAT changes in the visual cortices were not associated with tau or &bgr;-amyloid pathology in the occipital or the frontal, temporal, and parietal neocortex. However, the neocortical densities of LBs, particular those in BA17 and BAs18/19, correlated with lower synaptic and ChAT levels in these brain areas. These findings draw attention to molecular changes within the primary visual cortex in DLB and correlate with the neuroimaging findings within the occipital lobe in patients with this disorder.

Duplex ultrasound for the diagnosis of symptomatic deep vein thrombosis in the lower limb

This is the protocol for a review and there is no abstract. The objectives are as follows: To estimate the sensitivity and specificity of duplex ultrasound for the detection of distal and proximal DVT in symptomatic patients with prior testing by a clinical prediction rule (with or without additional D-dimer testing). The accuracy of ultrasound for DVT may be affected by body mass index and whether the patient has had a previous DVT. If possible, we shall investigate both previous DVT and body mass index as possible sources of heterogeneity, but recognise that these are patient-specific rather than study-specific characteristics. This means that results reported at the study level, for example average body mass index, may not be informative in an analysis and are more appropriately investigated with individual patient data. However, such an analysis may be possible if studies report results stratified by previous DVT status or body mass index. Two study-specific characteristics we shall investigate are the generation of the technology of the ultrasound scanner and type of reference standard: ascending venography, CT venography, or MR venography. Moreover, as the accuracy of duplex ultrasound depends on whether the DVT is distal or proximal, we shall perform separate meta-analyses according to site.

Type 2 diabetes: A side effect of the adaptation of neurons and fat cells to support increased cognitive performance

Type 2 diabetes is a serious disease that is affecting an increasing part of the population in most countries. A new hypothesis is presented in this paper about the underlying causes and mechanisms that lead to the development of this disease. It is proposed that the disease is the price that the organism pays for having improved cognitive performance that is achieved through increased level of neurite growth dynamics of neurons. The suggested mechanism of the disease development involves neural centres that deal with the sensing of fat and sugar levels in the blood and cerebro-spinal fluid, the regulation of the mobilisation of these resources in the body, the regulation of the storage of sugar and fat in the body, and the regulation of feeding behaviour. The key idea of the proposed mechanism is that the hypothesised resource mobilisation neural centre overestimates the resource needs of neurons and generates and inflated resource requesting signals. The paper discusses how short- and long-term equilibrium regulation of fat and sugar resources may emerge and how this regulation may get imbalanced leading to the emergence of type 2 diabetes in the animal or human. The paper proposes a number of experimental tests that can confirm or deny the validity of the hypothesis formulated here. Possible implications for development of new drugs aimed to prevent or reduce the negative impacts of type 2 diabetes are also discussed.

Catheter insertion techniques for improving catheter function and clinical outcomes in peritoneal dialysis patients

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to look at the benefits and harms of different PD catheter insertion techniques. 1. To establish whether a specific technique used to place catheters in adults and children, who are new to PD, result in any significant differences in clinical outcomes. Insertion techniques will be further defined as peritoneoscopic, percutaneous, fluoroscopic, laparoscopic insertion or open surgery. 2. To identify which technique offers optimal clinical outcomes and minimises post-procedure complications including postoperative haemorrhage, PD catheter dysfunction, exit site infection/peritonitis and bowel perforation.

Loss of synaptic proteins and choline acetyltransferase in primary and secondary visual cortex in dementia with Lewy bodies

Introduction: When 3 kDa soluble fluorescent dextran or 40 kDa ovalbumin are injected into the mouse striatum, they spread diffusely through the brain parenchyma and rapidly drain out of the brain along perivascular basement membranes surrounding capillaries and arteries. In the present study we test the hypothesis that immune complexes formed in the brain disrupt the perivascular drainage of solutes. Material and methods: Immune complexes were formed in the brain by actively immunizing mice against ovalbumin and then injecting ovalbumin intracerebrally. Twenty-four hours later dextran tracer was injected into the brain at the same site and animals killed 5 min and 3 h later. Results: At 5 min and 3 h after injection of the dextran tracer into the brains of immunized mice, immune complexes were located in the walls of arteries (as shown by Teeling et al. at this meeting). There was a significant reduction in the diffuse spread of dextran in the brain parenchyma and significantly fewer capillary and artery basement membranes contained dextran at 5 min when compared with the nonimmunized controls. Instead, the dextran tracer was concentrated in the perivenous spaces that were occupied by inflammatory cells. Conclusions: The results suggest that immune complexes disrupt and alter the pattern of perivascular drainage of solutes from the brain. This may have significance for inflammatory diseases in the brain and for immunotherapy for Alzheimer’s disease in which immune complexes may form and further block the perivascular drainage pathways that is already compromised by the deposition of amyloidbeta. This work is supported by the Alzheimer Research Trust.