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https://www.readbyqxmd.com/read/29453958/age-dependent-effects-of-dimethyl-fumarate-on-cognitive-and-neuropathological-features-in-the-streptozotocin-induced-rat-model-of-alzheimer-s-disease
#1
Irena Majkutewicz, Ewelina Kurowska, Magdalena Podlacha, Dorota Myślińska, Beata Grembecka, Jan Ruciński, Karolina Pierzynowska, Danuta Wrona
We previously demonstrated that dimethyl fumarate (DMF), an anti-oxidative and immunosuppresive compound, prevents intracerebroventricular (ICV) streptozotocin-induced disruption of spatial memory and neurodegeneration in 4-month-old rats. The present study evaluated the influence of age on DMF's therapeutic effect. Aged rats (22-months-old, n=40) were provided rodent chow containing DMF (0.4%) and given ICV injections of streptozotocin (STZ) or vehicle (Sham) on days 2 and 4. Spatial memory was evaluated using the Morris water maze (MWM) on days 14-21...
February 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29453245/early-vs-late-age-at-onset-frontotemporal-dementia-and-frontotemporal-lobar-degeneration
#2
Sang Won Seo, Marie-Pierre Thibodeau, David C Perry, Alice Hua, Manu Sidhu, Isabel Sible, Jose Norberto S Vargas, Stephanie E Gaus, Gil D Rabinovici, Katherine D Rankin, Adam L Boxer, Joel H Kramer, Howard J Rosen, Maria Luisa Gorno-Tempini, Lea T Grinberg, Eric J Huang, Stephen J DeArmond, John Q Trojanowski, Bruce L Miller, William W Seeley
OBJECTIVE: To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). METHODS: All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2)...
February 16, 2018: Neurology
https://www.readbyqxmd.com/read/29449700/imaging-tau-and-amyloid-%C3%AE-proteinopathies-in-alzheimer-disease-and-other-conditions
#3
REVIEW
Victor L Villemagne, Vincent Doré, Samantha C Burnham, Colin L Masters, Christopher C Rowe
Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Aβ-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-Aβ therapies both for patient recruitment and as an outcome measure. These studies have shown that Aβ accumulation is a protracted process that can extend for more than 2 decades before the onset of clinical AD...
February 16, 2018: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29449691/enhanced-release-of-acid-sphingomyelinase-enriched-exosomes-generates-a-lipidomics-signature-in-csf-of-multiple-sclerosis-patients
#4
Damiana Pieragostino, Ilaria Cicalini, Paola Lanuti, Eva Ercolino, Maria di Ioia, Mirco Zucchelli, Romina Zappacosta, Sebastiano Miscia, Marco Marchisio, Paolo Sacchetta, Marco Onofrj, Piero Del Boccio
Multiple Sclerosis (MuS) is a complex multifactorial neuropathology, resulting in heterogeneous clinical presentation. A very active MuS research field concerns the discovery of biomarkers helpful to make an early and definite diagnosis. The sphingomyelin pathway has emerged as a molecular mechanism involved in MuS, since high levels of ceramides in cerebrospinal fluid (CSF) were related to axonal damage and neuronal dysfunction. Ceramides are the hydrolysis products of sphingomyelins through a reaction catalyzed by a family of enzymes named sphingomyelinases, which were recently related to myelin repair in MuS...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449194/prostaglandin-d2-receptor-dp1-antibodies-predict-vaccine-induced-and-spontaneous-narcolepsy-type-1-large-scale-study-of-antibody-profiling
#5
Helle Sadam, Arno Pihlak, Anri Kivil, Susan Pihelgas, Mariliis Jaago, Priit Adler, Jaak Vilo, Olli Vapalahti, Toomas Neuman, Dan Lindholm, Markku Partinen, Antti Vaheri, Kaia Palm
BACKGROUND: Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or antigens for the immune response have, however, remained elusive. METHODS: Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA)...
February 2, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29448953/clinical-prevalence-of-lewy-body-dementia
#6
Joseph P M Kane, Ajenthan Surendranathan, Allison Bentley, Sally A H Barker, John-Paul Taylor, Alan J Thomas, Louise M Allan, Richard J McNally, Peter W James, Ian G McKeith, David J Burn, John T O'Brien
BACKGROUND: The prevalence of dementia with Lewy bodies (DLB) and dementia in Parkinson's disease (PDD) in routine clinical practice is unclear. Prevalence rates observed in clinical and population-based cohorts and neuropathological studies vary greatly. Small sample sizes and methodological factors in these studies limit generalisability to clinical practice. METHODS: We investigated prevalence in a case series across nine secondary care services over an 18-month period, to determine how commonly DLB and PDD cases are diagnosed and reviewed within two regions of the UK...
February 15, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29446949/positive-and-negative-allosteric-modulators-of-n-methyl-d-aspartate-nmda-receptors-structure-activity-relationships-and-mechanisms-of-action
#7
Erica S Burnell, Mark W Irvine, Guangyu Fang, Kiran Sapkota, David E Jane, Daniel T Monaghan
Excitatory activity in the CNS is predominately mediated by L-glutamate through several families of L-glutamate neurotransmitter receptors. Of these, the N-methyl-D-aspartate receptor (NMDAR) family has many critical roles in CNS function and in various neuropathological and psychiatric conditions. Until recently, the types of compounds available to regulate NMDAR function have been quite limited in terms of mechanism of action, subtype selectivity, and biological effect. However, several new classes of NMDAR agents have now been identified that are positive or negative allosteric modulators (PAMs and NAMs, respectively) with various patterns of NMDAR subtype selectivity...
February 15, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29445825/microglial-il-1%C3%AE-progressively-increases-with-duration-of-alcohol-consumption
#8
Bruno Pradier, Edda Erxlebe, Astrid Markert, Ildikó Rácz
Chronic alcohol abuse leads to severe brain damage. Although the underlying neuropathological processes are largely unknown, recent studies show that chronic alcohol consumption leads to neuroinflammation and may result in neurodegeneration and impaired neuronal connectivity. Long-term alcohol consumption promotes the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, and activates microglia cells in the brain. As it has not yet been investigated to what extent these processes dependent on the duration of alcohol consumption or whether microglia are source of pro-inflammatory cytokines in vivo, this study investigated the expression of the pro-inflammatory cytokine, IL-1β, in microglia at different time points in mice chronically exposed to alcohol...
February 14, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29444966/cerebral-microbleeds-and-csf-alzheimer-biomarkers-in-primary-progressive-aphasias
#9
Aline Mendes, Anne Bertrand, Foudil Lamari, Olivier Colliot, Alexandre Routier, Olivier Godefroy, Frédérique Etcharry-Bouyx, Olivier Moreaud, Florence Pasquier, Philippe Couratier, Karim Bennys, Martine Vercelletto, Olivier Martinaud, Bernard Laurent, Jérémie Pariente, Michèle Puel, Stéphane Epelbaum, Serge Belliard, Takoua Kaaouana, Ludovic Fillon, Marie Chupin, Bruno Dubois, Marc Teichmann
OBJECTIVE: To reveal the prevalence and localization of cerebral microbleeds (CMBs) in the 3 main variants of primary progressive aphasia (PPA) (logopenic, semantic, and nonfluent/agrammatic), to identify the relationship with underlying Alzheimer pathology, and to explore whether CMBs contribute to language breakdown. METHODS: We used a cross-sectional design in a multicenter cohort of 82 patients with PPA and 19 similarly aged healthy controls. MRI allowed for rating CMBs (2-dimensional gradient recalled echo T2*, susceptibility weighted imaging sequences) and white matter hyperintensities...
February 14, 2018: Neurology
https://www.readbyqxmd.com/read/29444314/diffuse-astrocytoma-idh-wildtype-a-dissolving-diagnosis
#10
Martin Hasselblatt, Mohammed Jaber, David Reuss, Oliver Grauer, Annkatrin Bibo, Stephanie Terwey, Uta Schick, Heinrich Ebel, Thomas Niederstadt, Walter Stummer, Andreas von Deimling, Werner Paulus
The histological and molecular features and even the mere existence of diffuse astrocytoma, IDH-wildtype, remain unclear. We therefore examined 212 diffuse astrocytomas (grade II WHO) in adults using IDH1(R132H) immunohistochemistry followed by IDH1/IDH2 sequencing and neuroimaging review. DNA methylation status and copy number profiles were assessed by Infinium HumanMethylation450k BeadChip. Only 25/212 patients harbored tumors without IDH1/IDH2 hotspot mutations and without contrast enhancement. By DNA methylation profiling, 10/25 tumors were classified as glioblastoma, IDH-wildtype, and an additional 7 cases could not be classified using methylome analysis, but showed genetic characteristics of glioblastoma...
February 9, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29442376/multiple-system-atrophy-and-apolipoprotein-e
#11
Kotaro Ogaki, Yuka A Martens, Michael G Heckman, Shunsuke Koga, Catherine Labbé, Oswaldo Lorenzo-Betancor, Anna I Wernick, Ronald L Walton, Alexandra I Soto, Emily R Vargas, Henrietta M Nielsen, Shinsuke Fujioka, Takahisa Kanekiyo, Ryan J Uitti, Jay A van Gerpen, William P Cheshire, Zbigniew K Wszolek, Phillip A Low, Wolfgang Singer, Dennis W Dickson, Guojun Bu, Owen A Ross
BACKGROUND: Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. OBJECTIVE: This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and α-synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect α-synuclein uptake in a oligodendrocyte cell...
February 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29441041/altered-brain-functional-connectome-in-migraine-with-and-without-restless-legs-syndrome-a-resting-state-functional-mri-study
#12
Fu-Chi Yang, Kun-Hsien Chou, Ai-Ling Hsu, Jong-Ling Fuh, Jiing-Feng Lirng, Hung-Wen Kao, Ching-Po Lin, Shuu-Jiun Wang
Background: Migraine is frequently comorbid with restless legs syndrome (RLS), both displaying functional connectivity (FC) alterations in multiple brain networks, although the neurological basis of this association is unknown. Methods: We performed resting-state functional magnetic resonance imaging and network-wise analysis of FC in migraine patients with and without RLS and healthy controls (CRL). Network-based statistics (NBS) and composite FC matrix analyses were performed to identify the patterns of FC changes...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29441010/an-aged-canid-with-behavioral-deficits-exhibits-blood-and-cerebrospinal-fluid-amyloid-beta-oligomers
#13
Clare Rusbridge, Francisco J Salguero, Monique Antoinette David, Kiterie M E Faller, Jose T Bras, Rita J Guerreiro, Angela C Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G P Brandner, Brian Summers, John Hardy, Mourad Tayebi
Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29440694/mutations-in-the-drosophila-homolog-of-human-pla2g6-give-rise-to-age-dependent-loss-of-psychomotor-activity-and-neurodegeneration
#14
Konstantin G Iliadi, Oxana B Gluscencova, Natalia Iliadi, Gabrielle L Boulianne
Infantile neuroaxonal dystrophy (INAD) is a fatal neurodegenerative disorder that typically begins within the first few years of life and leads to progressive impairment of movement and cognition. Several years ago, it was shown that >80% of patients with INAD have mutations in the phospholipase gene, PLA2G6. Interestingly, mutations in PLA2G6 are also causative in two other related neurodegenerative diseases, atypical neuroaxonal dystrophy and Dystonia-parkinsonism. While all three disorders give rise to similar defects in movement and cognition, some defects are unique to a specific disorder...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29439352/linking-atrial-fibrillation-with-alzheimer-s-disease-epidemiological-pathological-and-mechanistic-evidence
#15
Masafumi Ihara, Kazuo Washida
Many studies have shown a relationship between atrial fibrillation (AF) and vascular dementia. AF is a major risk factor for stroke, and stroke is the greatest risk factor for vascular dementia. However, the relationship between Alzheimer's disease (AD), the leading cause of dementia, and AF remains unclear. At least four epidemiological studies have reported AF significantly raises the risk of AD 1.5- to 2.5-fold. Chronic cerebral hypoperfusion, resulting from persistent AF, could explain the link as hypoperfusion may mechanistically exacerbate amyloid-β (Aβ) neuropathology, such as senile plaques and amyloid angiopathy, by upregulating Aβ-producing enzymes and lowering Aβ clearance efficiency...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439341/reproducibility-of-alzheimer-s-disease-cerebrospinal-fluid-biomarker-measurements-under-clinical-routine-conditions
#16
Jonathan Vogelgsang, Dirk Wedekind, Caroline Bouter, Hans-W Klafki, Jens Wiltfang
Analysis of cerebrospinal fluid (CSF) is one of the key tools for the state-of-the-art differential diagnosis of dementias. Dementia due to Alzheimer's disease (AD) is characterized by elevated CSF levels of total Tau (tTau) and phospho-181-Tau (pTau) and low CSF amyloid-β42 (Aβ42). Discrepancies in the laboratory analysis of human materials are well known and much effort has been put into harmonization procedures. In this study, we measured CSF biomarkers of more than 100 patients obtained under clinical routine conditions in two different clinical laboratories...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439329/subtle-cognitive-impairment-and-alzheimer-s-disease-type-pathological-changes-in-cerebrospinal-fluid-are-common-among-neurologically-healthy-subjects
#17
Fanni Haapalinna, Merja Kokki, Olli Jääskeläinen, Merja Hallikainen, Seppo Helisalmi, Anne Koivisto, Hannu Kokki, Teemu Paajanen, Janne Penttinen, Maria Pikkarainen, Minna Rautiainen, Hilkka Soininen, Eino Solje, Anne M Remes, Sanna-Kaisa Herukka
BACKGROUND: The neuropathology of Alzheimer's disease (AD) has previously been shown to be rather common among the elderly. OBJECTIVE: The aim of this study was to inspect the associations between cerebrospinal fluid (CSF) AD biomarker concentrations, age, the APOEɛ4 allele, cardiovascular diseases, diabetes, and cognitive performance in a cohort of a neurologically healthy population. METHODS: This study included 93 subjects (42 men, mean age 67 years) without previous neurological symptoms or subjective cognitive complaints...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439324/altered-expression-of-urea-cycle-enzymes-in-amyloid-%C3%AE-protein-precursor-overexpressing-pc12-cells-and-in-sporadic-alzheimer-s-disease-brain
#18
Henryk Jęśko, Walter J Lukiw, Anna Wilkaniec, Magdalena Cieślik, Magdalena Gąssowska-Dobrowolska, Emilia Murawska, Wojciech Hilgier, Agata Adamczyk
Urea cycle enzymes may play important yet poorly characterized roles in Alzheimer's disease (AD). Our previous results showed that amyloid-β (Aβ) affects urea cycle enzymes in rat pheochromocytoma (PC12) cells. The aim of the present study was to investigate the changes in arginases, other urea cycle enzymes, and nitric oxide synthases (NOSs) in PC12 cells transfected with AβPP bearing the double 'Swedish' mutation (APPsw, K670M/N671L) and in postmortem sporadic AD brain hippocampus; the mutation intensifies Aβ production and strongly associates with AD neuropathology...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29439247/mutual-relationship-between-tau-and-central-insulin-signalling-consequences-for-ad-and-tauopathies
#19
Maud Gratuze, Aurélie Joly-Amado, Didier Vieau, Luc Buée, David Blum
<br>Alzheimer's disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments and lower brain glucose metabolism, that often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood...
February 13, 2018: Neuroendocrinology
https://www.readbyqxmd.com/read/29439242/shared-molecular-neuropathology-across-major-psychiatric-disorders-parallels-polygenic-overlap
#20
Michael J Gandal, Jillian R Haney, Neelroop N Parikshak, Virpi Leppa, Gokul Ramaswami, Chris Hartl, Andrew J Schork, Vivek Appadurai, Alfonso Buil, Thomas M Werge, Chunyu Liu, Kevin P White, Steve Horvath, Daniel H Geschwind
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions...
February 9, 2018: Science
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