NEUE POLYDESMIDEN DES MUSEUMS BUITENZORG.

abstract not availabl

Rare histotype of sporadic Creutzfeldt-Jakob disease, clinically suspected as corticobasal degeneration

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disease that can mimic other neurological disorders. We present a case of sCJD in a 64-year-old man that presented with corticobasal syndrome and survived for 3 years. He presented initially with dementia, hemiparkinsonism and alien limb phenomenon and was diagnosed with corticobasal degeneration, ultimately progressing to immobility and akinetic mutism. With a normal MRI 1 year before onset, his neuroimaging 1 year later revealed abnormal DaTscan, cortical and hippocampal atrophy with ventricular dilatation on MRI, and diffusion-weighted cortical ribboning and thalamic hyperintensity. Postmortem, the patient’s brain was collected by the Parkinson’s UK Tissue Bank. Prion protein immunohistochemistry revealed widespread diffuse microvacuolar staining without kuru-type plaques. Hyperphosphorylated tau was only found in the entorhinal cortex and hippocampus. This case highlights the clinical heterogeneity of sCJD presentation and the important inclusion of CJD in the differential diagnosis of atypical presentations of neurodegenerative disease

Associations between multimorbidity and neuropathology in dementia: a case for considering functional cognitive disorders, psychiatric illness, and dementia mimics

Cognitive impairment in older people has a variety of underlying causes. In addition to neurodegenerative causes such as Alzheimer's disease, a dementia-like cognitive disorder may appear due to non-degenerative factors. Multimorbidity has been previously associated with clinical dementia risk, though whether this was due to greater risk of dementia-related neuropathology, or other factors that mimic dementia, was unclear. We provide evidence that physical multimorbidity is not associated with greater pathological changes at autopsy. Other factors related to multimorbidity and cognitive impairments may be important targets for investigation, such as functional cognitive disorders, primary psychiatric disorders (depression, anxiety, psychosis) and polypharmacy

Phase Transitions, Inhomogeneous Horizons and Second-Order Hydrodynamics

We use holography to study the spinodal instability of a four-dimensional, strongly-coupled gauge theory with a first-order thermal phase transition. We place the theory on a cylinder in a set of homogeneous, unstable initial states. The dual gravity configurations are black branes afflicted by a Gregory-Laflamme instability. We numerically evolve Einstein's equations to follow the instability until the system settles down to a stationary, inhomogeneous black brane. The dual gauge theory states have constant temperature but non-constant energy density. We show that the time evolution of the instability and the final states are accurately described by second-order hydrodynamics. In the static limit, the latter reduces to a single, second-order, non-linear differential equation from which the inhomogeneous final states can be derived

On Non-Commutative U*(1) Gauge Models and Renormalizability

Based on our recent findings regarding (non-)renormalizability of non-commutative U*(1) gauge theories [arxiv:0908.0467, arxiv:0908.1743] we present the construction of a new type of model. By introducing a soft breaking term in such a way that only the bilinear part of the action is modified, no interaction between the gauge sector and auxiliary fields occurs. Demanding in addition that the latter form BRST doublet structures, this leads to a minimally altered non-commutative U*(1) gauge model featuring an IR damping behavior. Moreover, the new breaking term is shown to provide the necessary structure in order to absorb the inevitable quadratic IR divergences appearing at one-loop level in theories of this kind. In the present paper we compute Feynman rules, symmetries and results for the vacuum polarization together with the one-loop renormalization of the gauge boson propagator and the three-point functions.Comment: 20 pages, 4 figures; v2-v4: clarified several points, and minor correction

A New Approach to Non-Commutative U(N) Gauge Fields

Based on the recently introduced model of arXiv:0912.2634 for non-commutative U(1) gauge fields, a generalized version of that action for U(N) gauge fields is put forward. In this approach to non-commutative gauge field theories, UV/IR mixing effects are circumvented by introducing additional 'soft breaking' terms in the action which implement an IR damping mechanism. The techniques used are similar to those of the well-known Gribov-Zwanziger approach to QCD.Comment: 11 pages; v2 minor correction

Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer's disease

Background: Basement membranes in the walls of cerebral capillaries and arteries form a major lymphatic drainage pathway for fluid and solutes from the brain. Amyloid-β (Aβ) draining from the brain is deposited in such perivascular pathways as cerebral amyloid angiopathy (CAA) in Alzheimer's disease (AD). CAA increases in severity when Aβ is removed from the brain parenchyma by immunotherapy for AD. In this study we investigated the consequences of immune complexes in artery walls upon drainage of solutes similar to soluble Aβ. We tested the hypothesis that, following active immunization with ovalbumin, immune complexes form within the walls of cerebral arteries and impair the perivascular drainage of solutes from the brain. Mice were immunized against ovalbumin and then challenged by intracerebral microinjection of ovalbumin. Perivascular drainage of solutes was quantified following intracerebral microinjection of soluble fluorescent 3kDa dextran into the brain at different time intervals after intracerebral challenge with ovalbumin. Results: Ovalbumin, IgG and complement C3 co-localized in basement membranes of artery walls 24 hrs after challenge with antigen; this was associated with significantly reduced drainage of dextran in immunized mice. Conclusions: Perivascular drainage along artery walls returned to normal by 7 days. These results indicate that immune complexes form in association with basement membranes of cerebral arteries and interfere transiently with perivascular drainage of solutes from the brain. Immune complexes formed during immunotherapy for AD may similarly impair perivascular drainage of soluble Aβ and increase severity of CAA

I-123-FP-CIT SPECT in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease: a new quantitative analysis of autopsy confirmed cases

Purpose The aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and Parkinson's disease (PD) using a quantitative analysis of I-123-FP-CIT SPECT scans.Methods Thirty-six patients with in vivo I-123-FP-CIT SPECT and neuropathological diagnoses were included. Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses. An additional 16 healthy controls (HC) scanned with I-123-FP-CIT SPECT were also included. All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians. Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR).Results Patients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD. Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB. Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously. No statistically significant differences were observed between the AD and HC.Conclusions This study demonstrates a very high diagnostic accuracy of the quantitative analysis of(I-123-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD.Neuro Imaging Researc

Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis.

Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival