Agomelatine Improves Apathy in Frontotemporal Dementia.
CONCLUSIONS: Our data, albeit preliminary, suggest that agomelatine could represent a novel useful approach to the treatment of apathy in FTD patients. PMID: 27229348 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - May 27, 2016 Category: Neurology Authors: Callegari I, Mattei C, Benassi F, Krueger F, Grafman J, Yaldizli Ö, Sassos D, Massucco D, Scialò C, Nobili F, Serrati C, Amore M, Cocito L, Emberti Gialloreti L, Pardini M Tags: Neurodegener Dis Source Type: research

Enhanced Detection and Sizing of the HTT CAG Repeat Expansion in Huntington Disease Using an Improved Triplet-Primed PCR Assay.
CONCLUSION: This method extends the detection limit of large expanded alleles to at least ∼175-180 CAG repeats, thus reducing the likelihood of requiring Southern blot analysis for any HD-affected sample. PMID: 27207688 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - May 21, 2016 Category: Neurology Authors: Zhao M, Lee CG, Law HY, Chong SS Tags: Neurodegener Dis Source Type: research

Ambulatory Activity Components Deteriorate Differently across Neurodegenerative Diseases: A Cross-Sectional Sensor-Based Study.
CONCLUSIONS: These findings provide objective evidence that reduced ambulatory activity is a shared feature across different NDDs. Moreover, they reveal that several underlying walking behavior components change with increasing disease duration, yet at a differing rate in different NDDs. This indicates that metric analysis of ambulatory activity might provide ecologically relevant and disease-specific progression and outcome markers in several NDDs. PMID: 27197840 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - May 21, 2016 Category: Neurology Authors: Klenk J, Srulijes K, Schatton C, Schwickert L, Maetzler W, Becker C, Synofzik M Tags: Neurodegener Dis Source Type: research

Human Senataxin Modulates Structural Plasticity of the Neuromuscular Junction in Drosophila through a Neuronally Conserved TGFβ Signalling Pathway.
CONCLUSIONS: The pan-neuronal expression of wild-type or mutant forms of hSETX induced morphological plasticity at neuromuscular junction (NMJ) synapses. Surprisingly, we found that while the NMJ synapses were increased in number, the neuronal function was normal. Analysis of signalling pathways revealed that hSETX modulates the Highwire (Hiw; a conserved neuronal E3 ubiquitin ligase)-dependent bone morphogenetic protein/TGFβ pathway. Thus, our study could pave the way for a better understanding of ALS4 progression by SETX through the regulation of neuronal E3 ubiquitin pathways. PMID: 27197982 [PubMed - as suppl...
Source: Neuro-Degenerative Diseases - May 21, 2016 Category: Neurology Authors: Mushtaq Z, Choudhury SD, Gangwar SK, Orso G, Kumar V Tags: Neurodegener Dis Source Type: research

Amyotrophic Lateral Sclerosis in Northern Spain 40 Years Later: What Has Changed?
CONCLUSION: After 3 decades, the annual incidence of ALS has almost doubled in our region. We did not find significant differences regarding other clinical or epidemiological features. PMID: 27188850 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - May 19, 2016 Category: Neurology Authors: Riancho J, Lozano-Cuesta P, Santurtún A, Sánchez-Juan P, López-Vega JM, Berciano J, Polo JM Tags: Neurodegener Dis Source Type: research

Preface.
PMID: 27002178 [PubMed - in process] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - March 24, 2016 Category: Neurology Authors: Fisher A, Nitsch RM, Windisch M Tags: Neurodegener Dis Source Type: research

Individual and Familial Susceptibility to MPTP in a Common Marmoset Model for Parkinson's Disease.
CONCLUSION: Our findings show that low-dose MPTP treatment in marmosets represents a clinically relevant PD model, with a window of opportunity to examine the onset of the disease, allowing the detection of individual variability in disease susceptibility, which may be of relevance for the diagnosis and treatment of PD in humans. PMID: 26999593 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - March 22, 2016 Category: Neurology Authors: Franke SK, van Kesteren RE, Hofman S, Wubben JA, Smit AB, Philippens IH Tags: Neurodegener Dis Source Type: research

Loss of Maspardin Attenuates the Growth and Maturation of Mouse Cortical Neurons.
CONCLUSIONS: Our current study uncovered a direct role for maspardin in normal and EGF-induced growth and maturation of primary cortical neurons. The loss of maspardin resulted in attenuated growth, axonal branching, and attenuation of EGF signaling. Reinstating the functions of maspardin may reverse hind limb impairment associated with neuronal dysfunction in mast syndrome patients. PMID: 26978163 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - March 16, 2016 Category: Neurology Authors: Davenport A, Bivona A, Latson W, Lemanski LF, Cheriyath V Tags: Neurodegener Dis Source Type: research

FP-CIT- and IBZM-SPECT in Corticobasal Syndrome: Results from a Clinical Follow-Up Study.
CONCLUSION: Our data indicate that in the early- to mid-stage CBS the degree of nigrostriatal impairment is only mild with a significant proportion of preserved dopamine transporter binding. PMID: 26978429 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - March 16, 2016 Category: Neurology Authors: Hammesfahr S, Antke C, Mamlins E, Beu M, Wojtecki L, Ferrea S, Dinkelbach L, Moldovan AS, Schnitzler A, Müller HW, Südmeyer M Tags: Neurodegener Dis Source Type: research

Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars.
CONCLUSIONS: The sperm and testicular degeneration of TgHD boars is caused by gain-of-function of the highly expressed mtHtt. PMID: 26959244 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - March 10, 2016 Category: Neurology Authors: Macakova M, Bohuslavova B, Vochozkova P, Pavlok A, Sedlackova M, Vidinska D, Vochyanova K, Liskova I, Valekova I, Baxa M, Ellederova Z, Klima J, Juhas S, Juhasova J, Klouckova J, Haluzik M, Klempir J, Hansikova H, Spacilova J, Collins R, Blumenthal I, Tal Tags: Neurodegener Dis Source Type: research

Alteration of Motor Protein Expression Involved in Bidirectional Transport in Peripheral Blood Mononuclear Cells of Patients with Amyotrophic Lateral Sclerosis.
CONCLUSION: In SALS, and especially in classic ALS, the changes in motor protein expression may alter bidirectional intracellular transport in PBMCs. More studies are needed to find out whether the levels of KIF5C and DCTN1 may be useful in ALS diagnosis, and whether KIF1B expression may discriminate ALS from ALS-mimicking disorders. PMID: 26954557 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - March 9, 2016 Category: Neurology Authors: Kuźma-Kozakiewicz M, Kaźmierczak B, Chudy A, Gajewska B, Barańczyk-Kuźma A Tags: Neurodegener Dis Source Type: research

Pharmacological or Genetic Activation of Hsp70 Protects against Loss of Parkin Function.
Abstract Mutations of parkin are a prevalent genetic contributor to familial Parkinson's disease (PD). As a key regulator of protein and mitochondrial homeostasis, parkin plays a pivotal role in maintaining dopaminergic neuronal survival. However, whereas Drosophila parkin null mutants exhibit prominent parkinsonian features, parkin-deficient mice generally lack an overt phenotype. Here, we found that the expression of Hsp70 along with several other members of the chaperone family is elevated in parkin null mice, suggesting a possible compensatory mechanism for the loss of parkin function in these mice that could ...
Source: Neuro-Degenerative Diseases - February 18, 2016 Category: Neurology Authors: Zhang CW, Adeline HB, Chai BH, Hong ET, Ng CH, Lim KL Tags: Neurodegener Dis Source Type: research

Population-Based Evidence that Survival in Amyotrophic Lateral Sclerosis Is Related to Weight Loss at Diagnosis.
CONCLUSION: More than 50% of ALS patients experience a WL of more than 5% at the time of diagnosis. This finding highlights the need for randomized trials to evaluate the effect of nutritional interventions to improve ALS survival. PMID: 26866503 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - February 12, 2016 Category: Neurology Authors: Marin B, Arcuti S, Jesus P, Logroscino G, Copetti M, Fontana A, Nicol M, Raymondeau M, Desport JC, Preux PM, Couratier P, French register of ALS in Limousin (FRALim) Tags: Neurodegener Dis Source Type: research

Integration of Intention and Outcome for Moral Judgment in Frontotemporal Dementia: Brain Structural Signatures.
CONCLUSIONS: Results suggest that moral judgment abnormalities in bvFTD are associated with impaired integration of intentions and outcomes, which depends on an extended brain network. In bvFTD, moral judgment seems to critically depend on areas beyond the VMPFC. PMID: 26859768 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - February 9, 2016 Category: Neurology Authors: Baez S, Kanske P, Matallana D, Montañes P, Reyes P, Slachevsky A, Matus C, Vigliecca NS, Torralva T, Manes F, Ibanez A Tags: Neurodegener Dis Source Type: research

Author Index Vol. 16, No. 1-2, 2016.
Authors: PMID: 26824235 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - January 30, 2016 Category: Neurology Tags: Neurodegener Dis Source Type: research

Subject Index Vol. 16, No. 1-2, 2016.
Authors: PMID: 26824367 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - January 30, 2016 Category: Neurology Tags: Neurodegener Dis Source Type: research

Preface.
Authors: PMID: 26824868 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - January 30, 2016 Category: Neurology Tags: Neurodegener Dis Source Type: research

Title Page / Table of Contents.
Authors: PMID: 26824932 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - January 30, 2016 Category: Neurology Tags: Neurodegener Dis Source Type: research

Measuring Global Brain Atrophy with the Brain Volume/Cerebrospinal Fluid Index: Normative Values, Cut-Offs and Clinical Associations.
Abstract BACKGROUND: Global brain atrophy is present in normal aging and different neurodegenerative disorders such as Alzheimer's disease (AD) and is becoming widely used to monitor disease progression. SUMMARY: The brain volume/cerebrospinal fluid index (BV/CSF index) is validated in this study as a measurement of global brain atrophy. We tested the ability of the BV/CSF index to detect global brain atrophy, investigated the influence of confounders, provided normative values and cut-offs for mild, moderate and severe brain atrophy, and studied associations with different outcome variables. A total of 1,009...
Source: Neuro-Degenerative Diseases - January 13, 2016 Category: Neurology Authors: Orellana C, Ferreira D, Muehlboeck JS, Mecocci P, Vellas B, Tsolaki M, Kłoszewska I, Soininen H, Lovestone S, Simmons A, Wahlund LO, Westman E, AddNeuronMed consortium and for the Alzheimer''s Disease Neuroimaging Initiative Tags: Neurodegener Dis Source Type: research

Cerebral β-Amyloid Angiopathy Is Associated with Earlier Dementia Onset in Alzheimer's Disease.
CONCLUSIONS: Our results suggest that CAA contributes to changes in early AD pathogenesis. This supports the idea that vascular change and neuritic plaque deposition are not just parallel processes but reflect additive pathological cascades that influence the course of clinical AD manifestation. Further inquiry into the role of CAA and its contribution to early cognitive change in AD is suggested. PMID: 26756746 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - January 13, 2016 Category: Neurology Authors: Vidoni ED, Yeh HW, Morris JK, Newell KL, Alqahtani A, Burns NC, Burns JM, Billinger SA Tags: Neurodegener Dis Source Type: research

BDNF Serum Levels with Respect to Multidimensional Assessment in Amyotrophic Lateral Sclerosis.
Abstract BACKGROUND: The clinical presentation of amyotrophic lateral sclerosis (ALS) is characterized by high heterogeneity, the greatest part of which still remains unexplained. OBJECTIVE: To assess serum levels of brain-derived neurotrophic factor (BDNF) in ALS patients, implementing a multidimensional characterization focused on four a priori chosen elements of phenotypic variability: ALS bulbar/spinal subtype, cognitive impairment, mood dysfunction and disease progression speed. METHODS: Serum samples were obtained from 45 ALS outpatients (16% bulbar onset) and 22 healthy controls. Each patient unde...
Source: Neuro-Degenerative Diseases - January 9, 2016 Category: Neurology Authors: Tremolizzo L, Pellegrini A, Conti E, Arosio A, Gerardi F, Lunetta C, Magni P, Appollonio I, Ferrarese C Tags: Neurodegener Dis Source Type: research

Low Serum Vitamin D Levels May Contribute to Gastric Dysmotility in de novo Parkinson's Disease.
Abstract BACKGROUND AND OBJECTIVES: Gastrointestinal dysfunction is a common non motor symptom in Parkinson's disease (PD). However, the potential association between vitamin D and gastroparesis in PD has not been previously investigated. The aim of this study was to compare vitamin D levels between drug-naive de novo PD patients with normal gastric emptying and those with delayed gastric emptying. METHODS: Fifty-one patients with drug-naive de novo PD and 20 age-matched healthy controls were enrolled in this study. Gastric emptying time (GET) was assessed by scintigraphy, and gastric emptying half-time (T1/2...
Source: Neuro-Degenerative Diseases - January 7, 2016 Category: Neurology Authors: Kwon KY, Jo KD, Lee MK, Oh M, Kim EN, Park J, Kim JS, Youn J, Oh E, Kim HT, Oh MY, Jang W Tags: Neurodegener Dis Source Type: research

PET Radioligands Reveal the Basis of Dementia in Parkinson's Disease and Dementia with Lewy Bodies.
Abstract BACKGROUND: Effective therapies for dementia with Lewy bodies (DLB) and Parkinson's disease (PD) dementia will require accurate diagnosis and an understanding of the contribution of distinct molecular pathologies to these diseases. We seek to use imaging biomarkers to improve diagnostic accuracy and to clarify the contribution of molecular species to cognitive impairment in DLB and PD. SUMMARY: We have performed cross-sectional and prospective cohort studies in subjects with DLB, PD with normal cognition, PD with mild cognitive impairment and PD with dementia, contrasted with Alzheimer's disease (AD)...
Source: Neuro-Degenerative Diseases - December 18, 2015 Category: Neurology Authors: Gomperts SN, Marquie M, Locascio JJ, Bayer S, Johnson KA, Growdon JH Tags: Neurodegener Dis Source Type: research

Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis.
Abstract BACKGROUND: There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. OBJECTIVE: In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. METHODS: Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the f...
Source: Neuro-Degenerative Diseases - December 16, 2015 Category: Neurology Authors: Nidos A, Kasselimis DS, Simos PG, Rentzos M, Alexakis T, Zalonis I, Zouvelou V, Potagas C, Evdokimidis I, Woolley SC Tags: Neurodegener Dis Source Type: research

Visual Assessment of Age-Related White Matter Hyperintensities Using FLAIR Images at 3 T: Inter- and Intra-Rater Agreement.
al FG Abstract BACKGROUND: Age-related white matter hyperintensities are frequent incidental findings on T2-weighted brain MRI, and they are evaluated in clinical practice using a visual rating scale. OBJECTIVE: To evaluate inter- and intra-rater agreement in MRI visual evaluations of age-related white matter hyperintensities made by two radiologists with different levels of experience using a visual rating scale. METHODS: Two radiologists of two different levels of experience separately rated age-related white matter hyperintensities in 40 consecutive 3-tesla brain MRI scans using the Fazekas and Schmid...
Source: Neuro-Degenerative Diseases - December 9, 2015 Category: Neurology Authors: Boutet C, Rouffiange-Leclair L, Schneider F, Camdessanché JP, Antoine JC, Barral FG Tags: Neurodegener Dis Source Type: research

Oxidized Docosahexaenoic Acid Species and Lipid Peroxidation Products Increase Amyloidogenic Amyloid Precursor Protein Processing.
n T Abstract One of the main characteristics of Alzheimer's disease (AD) is the β-amyloid peptide (Aβ) generated by β- and x03B3;-secretase processing of the amyloid precursor protein (APP). Previously it has been demonstrated that polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are associated with a reduced risk of AD caused by decreased Aβ production. However, in epidemiological studies and nutritional approaches, the outcomes of DHA-dependent treatment were partially controversial. PUFAs are very susceptible to reactive oxygen species and lipid peroxidation, which...
Source: Neuro-Degenerative Diseases - December 8, 2015 Category: Neurology Authors: Grimm MO, Haupenthal VJ, Mett J, Stahlmann CP, Blümel T, Mylonas NT, Endres K, Grimm HS, Hartmann T Tags: Neurodegener Dis Source Type: research

Do Beliefs about the Pathogenetic Role of Amyloid Affect the Interpretation of Amyloid PET in the Clinic?
CONCLUSIONS: This work supports an unbiased interpretation of amyloid PET across different beliefs about the pathogenic role of amyloid, and a belief-independent reluctance to change diagnosis in cases where change is expected and recommended. PMID: 26618706 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - December 1, 2015 Category: Neurology Authors: Boccardi M, Altomare D, Ferrari C, Festari C, Antelmi L, Pievani M, Tarallo A, Muscio C, Guerra UP, Paghera B, Padovani A, Frisoni GB, and the INDIA-FBP Working Group Tags: Neurodegener Dis Source Type: research

Insights into White Matter Damage in Alzheimer's Disease: From Postmortem to in vivo Diffusion Tensor MRI Studies.
CONCLUSIONS: AD is characterized by a relevant involvement of the WM as demonstrated by postmortem and in vivo evidence. WM microstructural damage in AD is not always secondary to neuronal loss, suggesting a role of other pathological mechanisms such as prion-like propagation of altered proteins or neuroinflammation. DT MRI offers new insight into AD pathophysiology and, more importantly, new possible targets for future experimental therapies. PMID: 26618812 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - December 1, 2015 Category: Neurology Authors: Caso F, Agosta F, Filippi M Tags: Neurodegener Dis Source Type: research

Iron in Frontotemporal Lobar Degeneration: A New Subcortical Pathological Pathway?
CONCLUSIONS: Our data suggest that H63D polymorphism could represent a disease-modifying gene in FTLD, fostering iron deposition in the basal ganglia. This suggests a new possible mechanism of FTLD-associated neurodegeneration. PMID: 26613252 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 28, 2015 Category: Neurology Authors: Gazzina S, Premi E, Zanella I, Biasiotto G, Archetti S, Cosseddu M, Scarpini E, Galimberti D, Serpente M, Gasparotti R, Padovani A, Borroni B Tags: Neurodegener Dis Source Type: research

No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study.
CONCLUSION: Our findings imply that the executive deficits which develop in some ALS patients emerge before motor symptoms and remain stable after an initial decline. The discrepancy between this trajectory and the progressive decline in motor functions may result from a differential vulnerability of motor and non-motor prefrontal neurons to the pathomechanism of ALS. PMID: 26613522 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 28, 2015 Category: Neurology Authors: Kasper E, Zydatiss K, Schuster C, Machts J, Bittner D, Kaufmann J, Benecke R, Vielhaber S, Teipel S, Prudlo J Tags: Neurodegener Dis Source Type: research

The Effect of Aβ1-42 Oligomers on APP Processing and Aβ1-40 Generation in Cultured U-373 Astrocytes.
CONCLUSIONS: These results suggest that activated astrocytes can contribute to the development of AD by enhancing levels and processing of APP leading to an increased production/secretion of Aβ-related peptides. PMID: 26606591 [PubMed - in process] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 27, 2015 Category: Neurology Authors: Ourdev D, Foroutanpay BV, Wang Y, Kar S Tags: Neurodegener Dis Source Type: research

Skewed X Inactivation in Women Carrying the FMR1 Premutation and Its Relation with Fragile-X-Associated Tremor/Ataxia Syndrome.
CONCLUSION: Although the reduced sample size and blood XCI patterns are two limitations of this study, our results suggest that the skewed XCI of the normal FMR1 allele may be a risk factor for the development of FXTAS. Furthermore, our findings also support the protective effect of the expression of a normal FMR1 allele. PMID: 26609701 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 27, 2015 Category: Neurology Authors: Alvarez-Mora MI, Rodriguez-Revenga L, Feliu A, Badenas C, Madrigal I, Milà M Tags: Neurodegener Dis Source Type: research

Differential Functional Connectivity Correlates of Cerebrospinal Fluid Biomarkers in Dementia of the Alzheimer's Type.
CONCLUSION: These results demonstrate the differential effects of AD biomarkers on functional connectivity networks, supporting a possible division of labour between the cardinal pathologies. PMID: 26610265 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 27, 2015 Category: Neurology Authors: Malpas CB, Saling MM, Velakoulis D, Desmond P, O''Brien TJ Tags: Neurodegener Dis Source Type: research

DYT6 Dystonia: A Neuropathological Study.
CONCLUSIONS: No neuropathological features that could be defined as hallmark features of DYT6 dystonia were identified. Our study supports the notion that in isolated dystonia, there is no significant neurodegeneration or morphological lesions that can be identified using routine methods. PMID: 26610312 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 27, 2015 Category: Neurology Authors: Paudel R, Li A, Hardy J, Bhatia KP, Houlden H, Holton J Tags: Neurodegener Dis Source Type: research

Inhibition of Pathogenic Mutant SOD1 Aggregation in Cultured Motor Neuronal Cells by Prevention of Its SUMOylation on Lysine 75.
Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective death of motor neurons. Mutations in the SOD1 gene encoding the superoxide dismutase 1 are present in 15% of familial ALS cases and in 2% of sporadic cases. These mutations are associated with the formation of SOD1-positive aggregates. The mechanisms of aggregation remain unknown, but posttranslational modifications of SOD1 may be involved. Here, we report that NSC-34 motor neuronal cells expressing mutant SOD1 contained aggregates positive for small ubiquitin modifier-1 (SUMO-1), and in parallel a redu...
Source: Neuro-Degenerative Diseases - November 26, 2015 Category: Neurology Authors: Dangoumau A, Marouillat S, Burlaud Gaillard J, Uzbekov R, Veyrat-Durebex C, Blasco H, Arnoult C, Corcia P, Andres CR, Vourc''h P Tags: Neurodegener Dis Source Type: research

Shared Molecular Mechanisms in Alzheimer's Disease and Amyotrophic Lateral Sclerosis: Neurofilament-Dependent Transport of sAPP, FUS, TDP-43 and SOD1, with Endoplasmic Reticulum-Like Tubules.
Abstract BACKGROUND: Amyotrophic lateral sclerosis (ALS), a debilitating neurodegenerative disorder of the motor neurons, leads to the disorganization of the neurofilament (NF) cytoskeleton and - ultimately - the deterioration of the neuromuscular junction. Some familial cases of ALS are caused by mutated FUS, TDP-43 or SOD1; it is thought that the mutated proteins inflict pathology either by gain or loss of function. The proper function of the neuromuscular junction requires sAPP, a soluble proteolytic fragment of the amyloid-β precursor protein (APP) - a transmembrane protein implicated in the pathology of ...
Source: Neuro-Degenerative Diseases - November 26, 2015 Category: Neurology Authors: Muresan V, Ladescu Muresan Z Tags: Neurodegener Dis Source Type: research

Levodopa-Induced Motor and Dopamine Receptor Changes in Caenorhabditis elegans Overexpressing Human Alpha-Synuclein.
CONCLUSIONS: This is the first report of changes in motor and dopamine receptors induced by levodopa in C. elegans overexpressing human α-synuclein. We propose that these phenotypes represent a simple animal model of LID in C. elegans. Such a model holds the promise of enabling high-throughput screenings for potential therapeutic targets and drug candidates. PMID: 26606044 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 26, 2015 Category: Neurology Authors: Gupta DK, Hang X, Liu R, Hasan A, Feng Z Tags: Neurodegener Dis Source Type: research

AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer's Disease.
AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer's Disease. Neurodegener Dis. 2015 Nov 26; Authors: Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E, LaFerla FM, Medeiros R Abstract We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic...
Source: Neuro-Degenerative Diseases - November 26, 2015 Category: Neurology Authors: Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E, LaFerla FM, Medeiros R Tags: Neurodegener Dis Source Type: research

Increased Mammalian Target of Rapamycin Signaling Contributes to the Accumulation of Protein Oxidative Damage in a Mouse Model of Down's Syndrome.
This study analyzed mTOR signaling in Ts65Dn mice, a model of DS, at 6 and 12 months of age compared with euploid mice showing the early aberrant hyperphosphorylation of mTOR coupled with the reduction of autophagosome formation. Moreover, the evaluation of protein oxidation shows an increase in protein nitration and protein-bound 4-hydroxynonenal in 12-month-old Ts65Dn mice suggesting the potential involvement of altered autophagy in the buildup of protein oxidative damage. In addition, data obtained on cell culture support the protective role of autophagy in reducing protein oxidation. Key Messages: Overall, this study p...
Source: Neuro-Degenerative Diseases - November 26, 2015 Category: Neurology Authors: Tramutola A, Lanzillotta C, Arena A, Barone E, Perluigi M, Di Domenico F Tags: Neurodegener Dis Source Type: research

Contents Vol. 15, 2015.
Authors: PMID: 26599358 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 24, 2015 Category: Neurology Tags: Neurodegener Dis Source Type: research

Lowered Levels of Carbonyl Proteins after Vitamin B Supplementation in Patients with Mild Cognitive Impairment and Alzheimer's Disease.
Abstract BACKGROUND: The critical role of neuro-inflammation and oxidative stress in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) has become evident. OBJECTIVE: The aim of this study is to assess the influence of vitamin supplementation on parameters of oxidative stress, inflammation as well as on cognition in patients with AD and mild cognitive impairment. METHODS: In our study, patients with cognitive impairment and healthy controls were enrolled. All patients were intended to receive vitamin supplementation (vitamin B1, B6, B12 and folic acid) for 3 months. Mini Ment...
Source: Neuro-Degenerative Diseases - November 21, 2015 Category: Neurology Authors: Rommer PS, Fuchs D, Leblhuber F, Schroth R, Greilberger M, Tafeit E, Greilberger J Tags: Neurodegener Dis Source Type: research

Discriminative Power of Arterial Spin Labeling Magnetic Resonance Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography Changes for Amyloid-β-Positive Subjects in the Alzheimer's Disease Continuum.
CONCLUSION: The results comparing measurements of CBF to CMRgl add to previous reports that MRI-measured CBF has a similar diagnostic ability to detect AD as has FDG-PET. Our findings that CBF and CMRgl changes occur in different brain regions in Aβ+ subjects across the AD continuum compared with Aβ- CN subjects may be the result of methodological differences. Alternatively, these findings may signal alterations in neurovascular coupling which alter relationships between brain perfusion and glucose metabolism in the AD continuum. PMID: 26560336 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 12, 2015 Category: Neurology Authors: Tosun D, Schuff N, Jagust W, Weiner MW, Alzheimer's Disease Neuroimaging Initiative Tags: Neurodegener Dis Source Type: research

Cerebrospinal Fluid Biomarkers Predict Clinical Evolution in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment.
CONCLUSION: An abnormal AD CSF biomarker profile in predementia subjects is a powerful predictor of cognitive and/or functional decline in the medium term. PMID: 26560503 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 12, 2015 Category: Neurology Authors: Sierra-Rio A, Balasa M, Olives J, Antonell A, Iranzo A, Castellví M, Bosch B, Grau-Rivera O, Fernandez-Villullas G, Rami L, Lladó A, Sánchez-Valle R, Molinuevo JL Tags: Neurodegener Dis Source Type: research

Genetic Disorders with Tau Pathology: A Review of the Literature and Report of Two Patients with Tauopathy and Positive Family Histories.
Abstract BACKGROUND: Tauopathies are a group of neurodegenerative disorders characterized by the pathological accumulation of hyperphosphorylated and insoluble tau protein within neurons and glia. Although most cases are sporadic, hereditary tauopathies have also been reported. SUMMARY: In this article, we review genetic disorders in which tau pathology has been reported and present two novel families with primary tauopathies. Mutations in the microtubule-associated protein tau gene (MAPT) cause a small subset of primary tauopathies. Mutations in 21 other genes and an 18q deletion syndrome have also been repo...
Source: Neuro-Degenerative Diseases - November 10, 2015 Category: Neurology Authors: Tacik P, Sanchez-Contreras M, Rademakers R, Dickson DW, Wszolek ZK Tags: Neurodegener Dis Source Type: research

Defining the Genetic Architecture of Alzheimer's Disease: Where Next?
Abstract BACKGROUND: Late-onset Alzheimer's disease is a genetically complex disorder. For 17 years, APOE was the only known susceptibility gene for disease. Through mostly genome-wide association studies, 25 loci are now known to associate with late-onset Alzheimer's disease. These susceptibility loci are not randomly distributed with respect to their functions. In fact, pathway analysis implicates significant enrichment of immunity, endocytosis, cholesterol metabolism, and ubiquitination in disease. SUMMARY: Twenty-five loci have now been reliably shown to associate with Alzheimer's disease. However, a sign...
Source: Neuro-Degenerative Diseases - November 10, 2015 Category: Neurology Authors: Sims R, Williams J Tags: Neurodegener Dis Source Type: research

Tau Immunotherapy.
Abstract In recent years, tau immunotherapy has advanced from proof-of-concept studies [Sigurdsson EM, NIH R01AG020197, 2001; Asuni AA, et al: J Neurosci 2007;27:9115-9129], which have now been confirmed and extended by us and others. Phase I clinical trials on active and passive tau immunizations are being conducted, with several additional passive tau antibody trials likely to be initiated in the near future for Alzheimer's disease and other tauopathies. Because tau pathology correlates better with the degree of dementia than amyloid-β (Aβ) pathology, greater clinical efficacy may be achieved by cleari...
Source: Neuro-Degenerative Diseases - November 10, 2015 Category: Neurology Authors: Sigurdsson EM Tags: Neurodegener Dis Source Type: research

Tau as the Converging Protein between Chronic Stress and Alzheimer's Disease Synaptic Pathology.
Abstract BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with a complex physiopathology and still undefined initiators. Several risk factors have been suggested for AD with recent evidence supporting an etiopathogenic role of chronic environmental stress and glucocorticoids (GCs, stress hormones) in the development of the disease. Indeed, both AD and chronic stress are associated with neuronal atrophy, synaptic loss and cognitive impairment. Our previous studies have demonstrated the aggravating role of stress and GCs on AD pathology, including Tau hyperphosphorylation and aggre...
Source: Neuro-Degenerative Diseases - November 10, 2015 Category: Neurology Authors: Sotiropoulos I, Sousa N Tags: Neurodegener Dis Source Type: research

Impaired Eukaryotic Elongation Factor 1A Expression in Alzheimer's Disease.
CONCLUSION: Dysregulation of eEF1A and its associated signaling pathways might represent novel molecular mechanisms underlying AD pathogenesis. Further investigation is necessary to determine whether eEF1A is a viable therapeutic target for AD and other cognitive syndromes. PMID: 26551858 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 10, 2015 Category: Neurology Authors: Beckelman BC, Zhou X, Keene CD, Ma T Tags: Neurodegener Dis Source Type: research

Higher Frequency and Complexity of Sleep Disturbances in Dementia with Lewy Bodies as Compared to Alzheimer's Disease.
CONCLUSIONS: Sleep problems are more common in DLB patients compared to AD, and are associated with more clinical impairment. DLB patients frequently have several sleep problems occurring simultaneously, which suggests a need for screening and accurate assessment of sleep in DLB. PMID: 26551998 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - November 10, 2015 Category: Neurology Authors: Chwiszczuk L, Breitve M, Hynninen M, Gjerstad MD, Aarsland D, Rongve A Tags: Neurodegener Dis Source Type: research

Clinicopathological Correlations and Concomitant Pathologies in Rapidly Progressive Dementia: A Brain Bank Series.
CONCLUSIONS: Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers. PMID: 26523804 [PubMed - as supplied by publisher] (Source: Neuro-Degenerative Diseases)
Source: Neuro-Degenerative Diseases - October 31, 2015 Category: Neurology Authors: Grau-Rivera O, Gelpi E, Nos C, Gaig C, Ferrer I, Saiz A, Lladó A, Molinuevo JL, Graus F, Sánchez-Valle R, Neurological Tissue Bank Collaborative Group Tags: Neurodegener Dis Source Type: research