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Jana Janssens, Yannick Vermeiren, Erik Fransen, Tony Aerts, Debby Van Dam, Sebastiaan Engelborghs, Peter P De Deyn
Introduction: Given the challenges concerning the differential diagnosis of dementia, we investigated the possible added value of monoaminergic compounds to the standard cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Particularly, regarding the AD versus dementia with Lewy bodies (DLB) comparison, monoamines or their metabolites might have added discriminative value as there is a more severe neuropathological burden in the locus coeruleus of DLB patients, the principal site of noradrenaline synthesis...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Syed M Hasan, Nida N Ahmed, Zunirah Ahmed, Allan Seibert
Amyloidosis is a rare disorder with a wide spectrum of presentations and anomalies. It is subdivided into 2 broad categories based on protein deposition; primary and secondary amyloidosis. It can present as a single-organ involvement or as a diffuse infiltrative multi-organ process. Isolated hepatic amyloidosis presentation is a rare phenomenon that develops due to insoluble amyloid deposition in liver. Its clinical presentation is usually vague and ranges from mild hepatomegaly with elevated liver enzymes to acute liver failure and hepatic rupture...
January 2018: Journal of Investigative Medicine High Impact Case Reports
Jun-Ichi Satoh, Yoshihiro Kino, Motoaki Yanaizu, Yuko Saito
Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by genetic mutations of either triggering receptor expressed on myeloid cells 2 ( TREM2 ) or TYRO protein tyrosine kinase binding protein ( TYROBP ), alternatively named DNAX-activation protein 12 ( DAP12 ), both of which are expressed on microglia in the brain and form the receptor-adaptor complex that chiefly recognizes anionic lipids. TREM2 transmits the signals involved in microglial survival, proliferation, chemotaxis, and phagocytosis...
February 2018: Intractable & Rare Diseases Research
Rachel Shikhman, Jarrod Curry, Roland Gazaille
Amyloidosis is a rare disease defined by accumulation of extracellular amyloid systemically or within a specific organ. Localized amyloidosis of the genitourinary system is extremely rare, with the predominate location being the bladder. The imaging findings are often nonspecific and mimic urothelial carcinoma. We present a 49-year-old woman with a chief complaint of flank pain. A filling defect was discovered on radiological imaging. The defect was subsequently biopsied and proven to be a primary amyloidosis of the renal pelvis...
February 2018: Radiology Case Reports
Liang Wei, Qi Wang, Yanfei Zhang, Cheng Yang, Hongxin Guan, Jianxin Jiang, Zhiyang Sun
Intracranial aneurysm (IA) is a localized dilation of the blood vessel. The present study was designed to explore the mechanisms of rupture of IA. GSE13353 (including 11 ruptured and 8 unruptured IA samples) and GSE15629 (including 8 ruptured and 6 unruptured IA samples) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) identified using limma and MetaDE packages were merged, and a protein-protein interaction (PPI) network analysis was performed using Cytoscape software...
April 2018: Oncology Letters
Srikant Rangaraju, Syed Ali Raza, Noel Xiang'An Li, Ranjita Betarbet, Eric B Dammer, Duc Duong, James J Lah, Nicholas T Seyfried, Allan I Levey
In the central nervous system (CNS), microglia are innate immune mononuclear phagocytes (CNS MPs) that can phagocytose infectious particles, apoptotic cells, neurons, and pathological protein aggregates, such as Aβ in Alzheimer's disease (AD). While CD11b+ CD45low microglia account for the majority of CNS MPs, a small population of CD11b+ CD45high CNS MPs is also recognized in AD that surround Aβ plaques. These transcriptionally and pathologically unique CD45high cells have unclear origin and undefined phagocytic characteristics...
2018: Frontiers in Immunology
Mathieu Verdurand, Elise Levigoureux, Sophie Lancelot, Waël Zeinyeh, Thierry Billard, Isabelle Quadrio, Armand Perret-Liaudet, Luc Zimmer, Fabien Chauveau
The accumulation of aggregated alpha-synuclein ( α -syn) in multiple brain regions is a neuropathological hallmark of synucleinopathies. Multiple system atrophy (MSA) is a synucleinopathy characterized by the predominant cerebral accumulation of aggregated α -syn as cytoplasmic glial inclusions (CGI). A premortem diagnosis tool would improve early diagnosis and help monitoring disease progression and therapeutic efficacy. One Positron Emission Tomography (PET) study suggested [11 C]BF-227 as a promising radiotracer for monitoring intracellular α -syn deposition in MSA patients...
2018: Contrast Media & Molecular Imaging
Yue Cao, Christian Hölscher, Meng-Ming Hu, Ting Wang, Fang Zhao, Yu Bai, Jun Zhang, Mei-Na Wu, Jin-Shun Qi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there is no cure. The early primary symptom of AD is the decline of memory ability, which gradually develops into complete dementia. Type 2 diabetes mellitus (T2DM) is an important risk factor of AD; and mimetics of the incretin hormone GLP-1 developed to treat diabetes are being tested as a novel therapeutic strategy for AD. In the present study, we reported for the first time the neuroprotective effects of a novel GLP-1/GIP dual agonist DA5-CH that activates the incretin hormone GLP-1 and GIP receptors in the APP/PS1 transgenic AD mouse model...
March 15, 2018: European Journal of Pharmacology
Varda Shoshan-Barmatz, Edna Nahon-Crystal, Anna Shteinfer-Kuzmine, Rajeev Gupta
Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Although an accumulation of brain amyloid-β (Aβ) peptide and hyperphosphorylated tau protein have been implicated in the pathogenesis of AD, the etiology of the disease remains unclear. Mitochondrial dysfunction has been identified as an early event in AD pathogenesis and is reflected by reduced metabolism, disruption of Ca2+ homeostasis, and increased levels of reactive oxygen species, lipid peroxidation, and apoptosis. The focus of this review is the involvement of mitochondrial dysfunction in AD, and specifically, the role of the voltage-dependent anion channel 1 (VDAC1), which has been linked to AD pathogenesis...
March 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Joshua T Byers, Xin Qing, Christopher Lo, Samuel W French, Ping Ji
Amyloidosis is a disorder characterized by the deposition of insoluble abnormal proteins in the extracellular space. It may occur as a localized lesion or as a systemic disease involving multiple organs and systems. Localized conjunctival amyloidosis is rare and is less frequently associated with systemic involvement. Although amyloidosis itself is a benign lesion involvement of multiple organs and systems is associated with poor prognosis. Diagnosis of amyloidosis is made on biopsy specimens with Congo red staining for the appearance of apple-green birefringence under polarized light microscopy...
March 15, 2018: Experimental and Molecular Pathology
Magdalena Martinez-Losa, Tara E Tracy, Keran Ma, Laure Verret, Alexandra Clemente-Perez, Abdullah S Khan, Inma Cobos, Kaitlyn Ho, Li Gan, Lennart Mucke, Manuel Alvarez-Dolado, Jorge J Palop
Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD...
March 15, 2018: Neuron
Carl Peter J Maury
A crucial stage in the origin of life was the emergence of the first molecular entity that was able to replicate, transmit information, and evolve on the early Earth. The amyloid world hypothesis posits that in the pre-RNA era, information processing was based on catalytic amyloids. The self-assembly of short peptides into β-sheet amyloid conformers leads to extraordinary structural stability and novel multifunctionality that cannot be achieved by the corresponding nonaggregated peptides. The new functions include self-replication, catalytic activities, and information transfer...
March 17, 2018: Cellular and Molecular Life Sciences: CMLS
Katarina Ulicna, Zuzana Bednarikova, Wei-Tse Hsu, Martina Holztragerova, Josephine W Wu, Slavka Hamulakova, Steven S-S Wang, Zuzana Gazova
Amyloid aggregates of proteins are one of the most abundant and important naturally occurring self-associated assemblies. Formation of poly/peptide amyloid aggregates is also associated with the widely spread diseases, so called amyloidosis, which include Alzheimer's disease, diabetes mellitus and lysozyme amyloidosis. These disorders are still incurable and novel therapeutical approaches are focused on using small molecules for inhibition of amyloid aggregation. We have observed effect of three structurally distinct groups of tacrine/acridone - coumarin heterodimers on hen egg white (HEW) lysozyme fibrillization in vitro...
March 9, 2018: Colloids and Surfaces. B, Biointerfaces
Xinwei Ge, Yunxiang Sun, Feng Ding
Accumulating evidence suggests that soluble oligomers are more toxic than final fibrils of amyloid aggregations. Among the mixture of inter-converting intermediates with continuous distribution of sizes and secondary structures, oligomers in the β-barrel conformation - a common class of protein folds with a closed β-sheet - have been postulated as the toxic species with well-defined three-dimensional structures to perform pathological functions. A common mechanism for amyloid toxicity, therefore, implies that all amyloid peptides should be able to form β-barrel oligomers as the aggregation intermediates...
March 14, 2018: Biochimica et Biophysica Acta
E A Horst, S K Kvidera, E J Mayorga, C S Shouse, M Al-Qaisi, M J Dickson, J Ydstie, H A Ramirez Ramirez, A F Keating, D J Dickson, K E Griswold, L H Baumgard
Activated immune cells are insulin sensitive and utilize copious amounts of glucose. Because chromium (Cr) increases insulin sensitivity and may be immunomodulatory, our objective was to evaluate the effect of supplemental Cr (KemTrace Cr propionate, 20 g/d; Kemin Industries Inc., Des Moines, IA) on immune system glucose utilization and immune system dynamics following an intravenous endotoxin challenge in lactating Holstein cows. Twenty cows (320 ± 18 d in milk) were randomly assigned to 1 of 4 treatments: (1) pair-fed (PF) control (PF-CON; 5 mL of saline; n = 5), (2) PF and Cr supplemented (PF-Cr; 5 mL of saline; n = 5), (3) lipopolysaccharide (LPS)-euglycemic clamp and control supplemented (LPS-CON; 0...
March 14, 2018: Journal of Dairy Science
Zhiqiang Jiang, Xiaoyan Dong, Yan Sun
Amyloid β-protein (Aβ) aggregation is crucial for the pathogenesis of Alzheimer's disease, and surface charge of nanoparticles (NPs) has been recognized as an important factor influencing Aβ aggregation. Herein, we report a systematic study on the issue with a series of self-assembled chitosan-hyaluronic acid composite (CH) NPs of different surface charges (CH1 to CH7, zeta potentials from +38 to -35 mV). Both the positive and negative CH NPs inhibited Aβ aggregation and the inhibitory effect increased with increasing the surface charges density...
March 8, 2018: Carbohydrate Research
Ruben Smith, Michael Schöll, Elisabet Londos, Tomas Ohlsson, Oskar Hansson
Mixed pathologies of α-synuclein, β-amyloid and tau are relatively common in Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). We therefore wanted to study the retention patterns of18 F-AV-1451 in PD, PD-dementia (PDD), and DLB. To do this 44 healthy controls, 11 non-demented patients with PD, 18 patients with PDD, and six patients with DLB underwent MRI and18 F-AV-1451 PET scanning and cognitive testing. We found that parietal18 F-AV-1451 retention was increased in patients with DLB compared to controls and PD patients, while18 F-AV-1451 uptake was reduced in the substantia nigra in PDD...
March 16, 2018: Scientific Reports
Timothy M Hughes, Lynne E Wagenknecht, Suzanne Craft, Akiva Mintz, Gerardo Heiss, Priya Palta, Dean Wong, Yun Zhou, David Knopman, Thomas H Mosley, Rebecca F Gottesman
OBJECTIVE: Arterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts. METHODS: The Atherosclerosis Risk in Communities (ARIC)-Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV])...
March 16, 2018: Neurology
Oscar L Lopez, Pauline Maillard
No abstract text is available yet for this article.
March 16, 2018: Neurology
J M G van Bergen, X Li, F C Quevenco, A F Gietl, V Treyer, R Meyer, A Buck, P A Kaufmann, R M Nitsch, P C M van Zijl, C Hock, P G Unschuld
The accumulation of β-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and β-amyloid plaques, and their possible association with cognitive performance in healthy older adults...
March 13, 2018: NeuroImage
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