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Lewy body disease

Taulant Muka, Lauren C Blekkenhorst, Joshua R Lewis, Richar L Prince, Nicole S Erler, Albert Hofman, Oscar H Franco, Fernando Rivadeneira, Jessica C Kiefte-de Jong
OBJECTIVE: We aimed to study whether dietary fat composition (n-3 and n-6 polyunsaturated fatty acids ratio (PUFAs) and PUFAs and saturated fatty acids (SFAs) ratio) is associated with total body fat (TF) and body fat distribution and whether this association was modified by the presence of chronic disease in middle-aged and elderly women in two population-based cohorts in the Netherlands and Australia. METHODS: The study was performed in the Rotterdam Study (RS), a prospective cohort study among subjects aged 55 years and older (N = 1182 women) and the Calcium Intake Fracture Outcome Study (CAIFOS), a 5-year randomized controlled trial among women age 70+ (N = 891)...
September 28, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Raquel Marin, Noemí Fabelo, Virginia Martín, Paula Garcia-Esparcia, Isidre Ferrer, David Quinto-Alemany, Mario Díaz
Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes...
September 6, 2016: Neurobiology of Aging
Darius Ebrahimi-Fakhari, Afshin Saffari, Lara Wahlster, Alessia Di Nardo, Daria Turner, Tommy L Lewis, Christopher Conrad, Jonathan M Rothberg, Jonathan O Lipton, Stefan Kölker, Georg F Hoffmann, Min-Joon Han, Franck Polleux, Mustafa Sahin
Tuberous sclerosis complex (TSC) is a neurodevelopmental disease caused by TSC1 or TSC2 mutations and subsequent activation of the mTORC1 kinase. Upon mTORC1 activation, anabolic metabolism, which requires mitochondria, is induced, yet at the same time the principal pathway for mitochondrial turnover, autophagy, is compromised. How mTORC1 activation impacts mitochondrial turnover in neurons remains unknown. Here, we demonstrate impaired mitochondrial homeostasis in neuronal in vitro and in vivo models of TSC...
October 18, 2016: Cell Reports
Tengfei Guo, Matthias Brendel, Timo Grimmer, Axel Rominger, Igor Yakushev
: Knowledge about spatial and temporal patterns of beta-amyloid (Aβ) accumulation is essential for understanding Alzheimer's disease (AD) and for design of anti-amyloid drug trials. Here, we tested if the regional pattern of longitudinal Aβ accumulation can be predicted by baseline amyloid PET. METHODS: Analyzed were baseline and 2 years follow-up (18)F-florbetapir PET data from 58 patients with incipient and manifest dementia due to Alzheimer's disease (AD). By determining how fast amyloid deposits in a given region relative to the whole brain grey matter, a pseudo-temporal accumulation rate for each region was calculated...
October 6, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Graham Fairfoul, Lynne I McGuire, Suvankar Pal, James W Ironside, Juliane Neumann, Sharon Christie, Catherine Joachim, Margaret Esiri, Samuel G Evetts, Michal Rolinski, Fahd Baig, Claudio Ruffmann, Richard Wade-Martins, Michele T M Hu, Laura Parkkinen, Alison J E Green
We have developed a novel real-time quaking-induced conversion RT-QuIC-based assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results...
October 2016: Annals of Clinical and Translational Neurology
Hye-Jin Park, Kang-Woo Lee, Eun S Park, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
OBJECTIVE: Protein phosphatase 2A (PP2A) is a heterotrimeric holoenzyme composed of a catalytic C subunit, a structural A subunit, and one of several regulatory B subunits that confer substrate specificity. The assembly and activity of PP2A are regulated by reversible methylation of the C subunit. α-Synuclein, which aggregates in Parkinson disease (PD) and dementia with Lewy bodies (DLB), is phosphorylated at Ser129, and PP2A containing a B55α subunit is a major phospho-Ser129 phosphatase...
October 2016: Annals of Clinical and Translational Neurology
Rainer von Coelln, Lisa M Shulman
PURPOSE OF REVIEW: Recent studies on clinical, genetic and pathological heterogeneity of Parkinson disease have renewed the old debate whether we should think of Parkinson disease as one disease with variations, or as a group of independent diseases that happen to present with similar phenotypes. Here, we provide an overview of where the debate is coming from, and how recent findings in clinical subtyping, genetics and clinico-pathological correlation have shaped this controversy over the last few years...
October 5, 2016: Current Opinion in Neurology
Alexandre N Rcom-H'cheo-Gauthier, Amelia Davis, Adrian C B Meedeniya, Dean L Pountney
α-Synuclein (α-syn) aggregates (Lewy bodies) in dementia with Lewy Bodies (DLB) may be associated with disturbed calcium homeostasis and oxidative stress. We investigated the interplay between α-syn aggregation, expression of the calbindin-D28k (CB) neuronal calcium-buffering protein and oxidative stress, combining immunofluorescence double labelling and Western analysis, and examining DLB and normal human cases and a unilateral oxidative stress lesion model of α-syn disease (rotenone mouse). DLB cases showed a greater proportion of CB+ cells in affected brain regions compared to normal cases with Lewy bodies largely present in CB- neurons and virtually undetected in CB+ neurons...
October 13, 2016: Molecular and Cellular Neurosciences
Pil Sung Gu, Minho Moon, Jin Gyu Choi, Myung Sook Oh
Mulberry fruit, which has been long used in traditional oriental medicine, was reported to ameliorate motor dysfunction and dopaminergic neuronal degeneration via antioxidant and antiapoptotic effects in an animal model of Parkinson's disease (PD). More than 95% of PD patients exhibit nonmotor problems such as olfactory dysfunction and gastrointestinal constipation, which are generally considered to be early symptoms of PD. However, few studies have actually examined potential drugs to treat early PD symptoms...
September 22, 2016: Journal of Nutritional Biochemistry
Koji Hori, Kimiko Konishi, Misa Hosoi, Hiroi Tomioka, Masayuki Tani, Yuka Kitajima, Mitsugu Hachisu
Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis...
2016: Parkinson's Disease
Venkatesh L Murthy, Siddique A Abbasi, Juned Siddique, Laura A Colangelo, Jared Reis, Bharath A Venkatesh, J Jeffrey Carr, James G Terry, Sarah M Camhi, Michael Jerosch-Herold, Sarah de Ferranti, Saumya Das, Jane Freedman, Mercedes R Carnethon, Cora E Lewis, Joao A C Lima, Ravi V Shah
BACKGROUND: Despite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk, current guidelines focus on risk assessments later in life, missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease. METHODS AND RESULTS: In 4420 young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we defined a "metabolic" risk score based on components of the Third Report of the Adult Treatment Panel's definition of metabolic syndrome...
October 13, 2016: Journal of the American Heart Association
Dhiman Ghosh, Surabhi Mehra, Shruti Sahay, Pradeep K Singh, Samir K Maji
Parkinson's disease (PD) is a neurological disorder marked by the presence of cytoplasmic inclusions, Lewy bodies (LBs) and Lewy neurites (LNs) as well as the degeneration of dopamine producing neurons in the substantia nigra region of the brain. The LBs and LNs in PD are mainly composed of aggregated form of a presynaptic protein, α-synuclein (α-Syn). However, the mechanisms of α-Syn aggregation and actual aggregated species responsible for the degeneration of dopaminergic neurons have not yet been resolved...
October 10, 2016: International Journal of Biological Macromolecules
Marthe H R Ludtmann, Plamena R Angelova, Natalia N Ninkina, Sonia Gandhi, Vladimir L Buchman, Andrey Y Abramov
: Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Tamara Shiner, Anat Mirelman, Mali Gana Weisz, Anat Bar-Shira, Elissa Ash, Ron Cialic, Naomi Nevler, Tanya Gurevich, Noa Bregman, Avi Orr-Urtreger, Nir Giladi
Importance: Mutations in the glucocerebrosidase (GBA) gene are a risk factor for the development of dementia with Lewy bodies (DLB). These mutations are common among Ashkenazi Jews (AJ) and appear to have an effect on the natural history of the disease. Objectives: To evaluate the clinical and genetic characteristics of an AJ cohort of patients diagnosed with DLB, assess the association of phenotype of DLB with GBA mutations, and explore the effects of these mutations on the clinical course of the disease...
October 10, 2016: JAMA Neurology
T A Polyakova, O S Levin
AIM: To study a role of cerebral microbleeds (CMB) in the diagnosis of main cerebrovascular and neurodegenerative diseases with cognitive impairment. MATERIAL AND METHODS: CMB were studied in 120 patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and vascular dementia using 1.5T MRI in T2 * gradient echo. An impact of CMB on cognitive functions and the relationship with signs of vascular and neurodegenerative lesions of the brain were studied as well...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Meenakshi Dauwan, Jessica J van der Zande, Edwin van Dellen, Iris E C Sommer, Philip Scheltens, Afina W Lemstra, Cornelis J Stam
INTRODUCTION: The aim of this study was to build a random forest classifier to improve the diagnostic accuracy in differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) and to quantify the relevance of multimodal diagnostic measures, with a focus on electroencephalography (EEG). METHODS: A total of 66 DLB, 66 AD patients, and 66 controls were selected from the Amsterdam Dementia Cohort. Quantitative EEG (qEEG) measures were combined with clinical, neuropsychological, visual EEG, neuroimaging, and cerebrospinal fluid data...
2016: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Andrea Lee, Rebecca M Gilbert
Parkinson disease (PD) is a common progressive neurodegenerative condition, causing both motor and non motor symptoms. Motor symptoms include stiffness, slowness, rest tremor and poor postural reflexes, whereas nonmotor symptoms include abnormalities of mood, cognition, sleep and autonomic function. Affected patients show cell loss in the substantia nigra pars compacta, and accumulation of aggregated alpha-synuclein into intracellular structures called Lewy bodies, within specific brain regions. The main known non modifiable risk factor is age...
November 2016: Neurologic Clinics
P S Jairani, P M Aswathy, Srinivas Gopala, Joe Verghese, P S Mathuranath
BACKGROUND: This study delineates the role of the interaction of apolipoprotein E (APOE) and MAPT alleles in contributing to disease risks of dementia in a southern Indian population. METHODS: A sample of 419 patients comprising Alzheimer's disease (AD; n = 156), mild cognitive impairment (MCI; n = 87), frontotemporal dementia (FTD; n = 127), vascular dementia (VD; n = 37), and dementia with Lewy bodies (DLB; n = 12) was analysed in comparison with a control group (n = 138)...
October 6, 2016: Dementia and Geriatric Cognitive Disorders
Yoshihide Takeshita, Nobuto Shibata, Koji Kasanuki, Tomoyuki Nagata, Shunichiro Shinagawa, Nobuyuki Kobayashi, Tohru Ohnuma, Ayako Suzuki, Eri Kawai, Toshiki Takayama, Kenya Nishioka, Yumiko Motoi, Nobutaka Hattori, Kazuhiko Nakayama, Hisashi Yamada, Heii Arai
BACKGROUND/AIMS: Interaction of receptor for advanced glycation end products (RAGE) with amyloid-β increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. METHODS: Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls...
October 4, 2016: International Journal of Geriatric Psychiatry
Karen Manoutcharian, Roxanna Perez-Garmendia, Goar Gevorkian
Recombinant antibody fragments are promising alternatives to full-length immunoglobulins and offer important advantages compared with conventional monoclonal antibodies: extreme specificity, higher affinity, superior stability and solubility, reduced immunogenicity as well as easy and inexpensive large-scale production. Different antibody formats such as single-chain fragment variable (scFv), single-domain antibody fragments (VHHs or sdAbs), bispecific antibodies (bsAbs), intrabodies and nanobodies, are currently being studied in pre-clinical models of cancer as well as infectious and autoimmune diseases and many of them are being tested as therapeutics in clinical trials...
September 30, 2016: Current Neuropharmacology
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