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Familial Alzheimer's disease

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https://www.readbyqxmd.com/read/29775139/burden-and-strain-among-familial-caregivers-of-patients-with-dementia-in-china
#1
Min Zhang, Yu-Ping Chang, Yu Jin Liu, Ling Gao, Davina Porock
BACKGROUND: Alzheimer's disease is one of a variety of progressive and ultimately fatal neurodegenerative diseases that are characterized by a number of nervous and mental symptoms and behavior disorders. These problems are likely to cause burden and strain on caregivers. In this study, we demonstrated the level and relationship of burden and strain among caregivers of dementia patients in China. METHODS: A total of 212 caregivers of family members with dementia responded to the survey...
May 2018: Issues in Mental Health Nursing
https://www.readbyqxmd.com/read/29772554/antibodies-against-gpcr
#2
Carlotto Meyer, Harald Heidecke
G-protein-coupled receptors (GPCRs) are the largest family of receptors in humans. GPCRs are seven-transmembrane receptors that are activated by the binding of a ligand to the extracellular domain. In addition to the endogenous ligands, auto-antibodies (aab) can also bind to the GPCRs. They can activate different and specific cellular pathways which contribute to various diseases. In this review, the authors summarize the knowledge about antibodies targeting GPCRs and their effects and relevance in the pathogenesis of various diseases and their use in clinical diagnostics...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770145/-%C3%AE-carboline-silver-compound-binding-studies-with-human-serum-albumin-a-comprehensive-multispectroscopic-analysis-and-molecular-modeling-study
#3
Ali Alsalme, Rais Ahmad Khan, Arwa M Alkathiri, Mohd Sajid Ali, Sartaj Tabassum, Mohammed Jaafar, Hamad A Al-Lohedan
β -Carbolines ( β Cs) belong to the naturally occurring alkaloid family, derived from 9H-pyrido[3,4-b]indole, also known as norharmane (Hnor). Knowing the importance of the β Cs alkaloid family in biological processes, a comprehensive binding study is reported of four Ag(I) compounds containing the ligand Hnor and having different counteranions, namely, NO3 - , ClO4 - , BF4 - , and PF6 - , with human serum albumin (HSA) as a model protein. Different approaches like UV-visible, fluorescence spectroscopy, circular dichroism (CD), and molecular docking studies have been used for this purpose...
2018: Bioinorganic Chemistry and Applications
https://www.readbyqxmd.com/read/29762014/selective-and-sensitive-pull-down-of-amyloid-fibrils-produced-in-vitro-and-in-vivo-by-the-use-of-pentameric-thiophene-coupled-resins
#4
Anna Beatriz Wreden, Luiza Fernandes, Mirian Kelley, Antônio Pereira-Neves, Caroline S Moreira, David R da Rocha, Fernando L Palhano
Protein aggregation is a hallmark of several degenerative diseases, including Alzheimer's disease, Parkinson's disease and familial amyloidosis (Finnish type) (FAF). A method to isolate and detect amyloids is desired for the diagnosis of amyloid diseases. Here, we report the synthesis of pentameric thiophene amyloid ligand (p-FTAA) linked to agarose resin for selective purification of amyloid aggregates produced in vitro and in vivo. Using amyloid fibrils produced in vitro from alpha-synuclein, gelsolin and Aβ1-40 and gelsolin amyloid aggregates extracted from tissue homogenates of a mouse model of FAF, we observed that p-FTAA resin was able to pull down amyloid aggregates...
May 15, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29758318/proteome-and-behavioral-alternations-in-phosphorylation-deficient-mutant-collapsin-response-mediator-protein2-knock-in-mice
#5
Haruko Nakamura, Aoi Takahashi-Jitsuki, Hiroko Makihara, Tetsuya Asano, Yayoi Kimura, Jun Nakabayashi, Naoya Yamashita, Yuko Kawamoto, Fumio Nakamura, Toshio Ohshima, Hisashi Hirano, Fumiaki Tanaka, Yoshio Goshima
CRMP2, alternatively designated as DPYSL2, was the first CRMP family member to be identified as an intracellular molecule mediating the signaling of the axon guidance molecule Semaphorin 3A (Sema3A). In Sema3A signaling, cyclin-dependent kinase 5 (Cdk5) primarily phosphorylates CRMP2 at Ser522. Glycogen synthase kinase-3β (GSK-3β) subsequently phosphorylates the residues of Thr509 and Thr514 of CRMP2. Previous studies showed that CRMP2 is involved in pathogenesis of neurological disorders such as Alzheimer's disease...
May 11, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29755340/glutamate-transporter-glt1-expression-in-alzheimer-disease-and-dementia-with-lewy-bodies
#6
Paula Garcia-Esparcia, Daniela Diaz-Lucena, Marina Ainciburu, Benjamin Torrejón-Escribano, Margarita Carmona, Franc Llorens, Isidro Ferrer
Glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2), a major modulator of glutamate homeostasis in astrocytes, is assessed in post-mortem human brain samples of frontal cortex area 8 in advanced stages of Alzheimer disease (AD) and terminal stages of dementia with Lewy bodies (DLB) in order to gain understanding of astrogliopathy in diseases manifested by dementia. Glial fibrillary acidic protein (GFAP) mRNA expression is significantly increased in AD but not in DLB, whereas GLT1 , vesicular glutamate transporter 1 ( vGLUT1 ) and aldehyde dehydrogenase 1 family member 1 ( ALDH1L1 ) are not modified in AD and DLB when compared with controls...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29751080/prenylated-%C3%AE-diketones-two-new-additions-to-the-family-of-biologically-active-hypericum-perforatum-l-hypericaceae-secondary-metabolites
#7
Niko S Radulović, Marija S Genčić, Nikola M Stojanović, Pavle J Randjelović, Nicolas Baldovini, Vanya Kurteva
Two novel β-diketones, 2,6,9-trimethyl-8-decene-3,5-dione (A) and 3,7,10-trimethyl-9-undecene-4,6-dione (B), were identified from the renowned medicinal plant Hypericum perforatum L. The structures of β-diketones A and B were corroborated by syntheses (4 steps starting from methyl acetoacetate, overall yields 30% and 23%, respectively). In solution, these β-diketones predominantly exist as two rapidly interconverting β-keto-enol tautomers. The structures of A and B show some common fragments with the molecules of hyperforin and adhyperforin, respectively, the acknowledged multi-target secondary metabolites from St...
May 8, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29747683/reduced-penetrance-of-the-psen1-h163y-autosomal-dominant-alzheimer-mutation-a-22-year-follow-up-study
#8
Steinunn Thordardottir, Elena Rodriguez-Vieitez, Ove Almkvist, Daniel Ferreira, Laure Saint-Aubert, Anne Kinhult-Ståhlbom, Håkan Thonberg, Michael Schöll, Eric Westman, Anders Wall, Maria Eriksdotter, Henrik Zetterberg, Kaj Blennow, Agneta Nordberg, Caroline Graff
BACKGROUND: The range of onset ages within some PSEN1 families is wide, and a few cases of reduced penetrance of PSEN1 mutations have been reported. However, published data on reduced penetrance have been limited to clinical histories, often collected retrospectively and lacking biomarker information. We present a case of reduced penetrance of the PSEN1 H163Y mutation in a carrier prospectively followed for 22 years. METHODS: Two brothers (A and B), both carriers of the H163Y mutation, were followed between 1995 and 2017...
May 10, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29746584/specific-serum-and-csf-microrna-profiles-distinguish-sporadic-behavioural-variant-of-frontotemporal-dementia-compared-with-alzheimer-patients-and-cognitively-healthy-controls
#9
Johannes Denk, Felix Oberhauser, Johannes Kornhuber, Jens Wiltfang, Klaus Fassbender, Matthias L Schroeter, Alexander E Volk, Janine Diehl-Schmid, Johannes Prudlo, Adrian Danek, Bernhard Landwehrmeyer, Martin Lauer, Markus Otto, Holger Jahn
Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results...
2018: PloS One
https://www.readbyqxmd.com/read/29738527/defensive-effect-of-microrna-200b-c-against-amyloid-beta-peptide-induced-toxicity-in-alzheimer-s-disease-models
#10
Sayuri Higaki, Masashi Muramatsu, Akio Matsuda, Kenji Matsumoto, Jun-Ichi Satoh, Makoto Michikawa, Shumpei Niida
MiRNA molecules are important post-transcriptional regulators of gene expression in the brain function. Altered miRNA profiles could represent a defensive response against the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD). Endogenous miRNAs have lower toxic effects than other gene silencing methods, thus enhancing the expression of defensive miRNA could be an effective therapy. However, little is known about the potential of targeting miRNAs for the treatment of AD. Here, we examined the function of the miR-200 family (miR-200a, -141, -429, -200b, -200c), identified using miRNA microarray analysis of cortical tissue from Tg2576 transgenic mice...
2018: PloS One
https://www.readbyqxmd.com/read/29735432/the-retina-as-a-window-to-early-dysfunctions-of-alzheimer-s-disease-following-studies-with-a-5xfad-mouse-model
#11
Chiara Criscuolo, Elisa Cerri, Carlotta Fabiani, Simona Capsoni, Antonino Cattaneo, Luciano Domenici
Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to neuronal dysfunctions with cognitive impairment. AD can affect visual pathways and visual cortex and result in various visual changes and problems. However, how early the visual dysfunctions occur in AD is still a matter of discussion. Here, we used electrophysiological techniques to show the presence of early anomalies in AD visual system. To this aim, we used a familial AD (FAD) model, the 5xFAD transgenic mouse, characterized by severe progressive amyloid pathology and cognitive deficits...
March 23, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29735156/subjective-cognitive-decline-is-associated-with-altered-default-mode-network-connectivity-in-individuals-with-a-family-history-of-alzheimer-s-disease
#12
Sander C J Verfaillie, Alexa Pichet Binette, Etienne Vachon-Presseau, Shirin Tabrizi, Mélissa Savard, Pierre Bellec, Rik Ossenkoppele, Philip Scheltens, Wiesje M van der Flier, John C S Breitner, Sylvia Villeneuve
BACKGROUND: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. METHODS: We studied 124 asymptomatic individuals with a family history of AD (age 64 ± 5 years)...
May 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
https://www.readbyqxmd.com/read/29734820/family-history-of-alzheimer-s-disease-and-subjective-memory-performance
#13
Robert Haussmann, Steffi Ganske, Antonia Gruschwitz, Annett Werner, Antje Osterrath, Jan Lange, Maria Buthut, Katharina L Donix, Jennifer Linn, Markus Donix
People with a first-degree family history of Alzheimer's disease are at an increased risk of developing dementia. Subjective memory impairment among individuals with no measurable cognitive deficits may also indicate elevated dementia risk. It remains unclear whether nondemented people with a positive family history of Alzheimer's disease are more likely to experience cognitive deficits and whether such an association reflects underlying neuropathology. We therefore investigated subjective memory impairment and hippocampal cortical thickness in 40 healthy older adults and 35 patients with amnestic mild cognitive impairment...
January 1, 2018: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/29734098/investigation-of-possible-risk-factors-for-depression-in-alzheimer-s-disease-a-systematic-review-of-the-evidence
#14
REVIEW
Natassa Steck, Claudia Cooper, Vasiliki Orgeta
BACKGROUND: Depression is common in people with Alzheimer's disease (AD), and is associated with increased risk of institutionalization and mortality. Understanding risk factors for depression in AD is key to its development and treatment. METHODS: We searched the MEDLINE, EMBASE, PsycINFO, and CINAL databases for longitudinal prospective cohort studies that evaluated risk factors for depression in people with AD. Two authors independently selected articles for inclusion and assessed quality of studies using predetermined criteria...
April 10, 2018: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29729423/interaction-between-a-mapt-variant-causing-frontotemporal-dementia-and-mutant-app-affects-axonal-transport
#15
Robert Adalbert, Stefan Milde, Claire Durrant, Kunie Ando, Virginie Stygelbout, Zehra Yilmaz, Stacey Gould, Jean-Pierre Brion, Michael P Coleman
In Alzheimer's disease, many indicators point to a central role for poor axonal transport, but the potential for stimulating axonal transport to alleviate the disease remains largely untested. Previously, we reported enhanced anterograde axonal transport of mitochondria in 8- to 11-month-old MAPTP301L knockin mice, a genetic model of frontotemporal dementia with parkinsonism-17T. In this study, we further characterized the axonal transport of mitochondria in younger MAPTP301L mice crossed with the familial Alzheimer's disease model, TgCRND8, aiming to test whether boosting axonal transport in young TgCRND8 mice can alleviate axonal swelling...
April 5, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29729307/virgin-coconut-oil-vco-by-normalizing-nlrp3-inflammasome-showed-potential-neuroprotective-effects-in-amyloid-%C3%AE-induced-toxicity-and-high-fat-diet-fed-rat
#16
Fatemeh Mirzaei, Mozafar Khazaei, Alireza Komaki, Iraj Amiri, Cyrus Jalili
Both dyslipidemia and Alzheimer disease (AD) are associated with aging. In this study, the effects of virgin coconut oil (VCO) on inflammasome and oxidative stress in Alzheimer's model (receiving Amyloid-β (Aβ)) and high-fat diet (HFD) model were determined. A total of 120 male Wistar rats, were divided into 12 groups (n = 10), including; healthy control, sham surgery, sham surgery receiving normal saline, HFD, HFD + 8% VCO, HFD + 10% VCO, Aβ received rats, Aβ + 8%VCO, Aβ + 10%VCO, HFD + Aβ, HFD + Aβ+8%VCO, and HFD + Aβ + 10%VCO...
May 2, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29725045/solvation-guided-design-of-fluorescent-probes-for-discrimination-of-amyloids
#17
Kevin J Cao, Kristyna M Elbel, Jessica L Cifelli, Jordi Cirera, Christina J Sigurdson, Francesco Paesani, Emmanuel A Theodorakis, Jerry Yang
The deposition of insoluble protein aggregates in the brain is a hallmark of many neurodegenerative diseases. While their exact role in neurodegeneration remains unclear, the presence of these amyloid deposits often precedes clinical symptoms. As a result, recent progress in imaging methods that utilize amyloid-specific small molecule probes have become a promising avenue for antemortem disease diagnosis. Here, we present a series of amino-aryl cyanoacrylate (AACA) fluorophores that show a turn-on fluorescence signal upon binding to amyloids in solution and in tissue...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29725009/smpd3-deficiency-perturbs-neuronal-proteostasis-and-causes-progressive-cognitive-impairment
#18
Wilhelm Stoffel, Britta Jenke, Inga Schmidt-Soltau, Erika Binczek, Susanne Brodesser, Ina Hammels
Neutral sphingomyelinase smpd3 is most abundantly expressed in neurons of brain. The function of SMPD3 has remained elusive. Here, we report a pathogenetic nexus between absence of SMPD3 in the Golgi compartment (GC) of neurons of the smpd3-/- mouse brain, inhibition of Golgi vesicular protein transport and progressive cognitive impairment. Absence of SMPD3 activity in the Golgi sphingomyelin cycle impedes remodeling of the lipid bilayer, essential for budding and multivesicular body formation. Importantly, we show that inhibition of the Golgi vesicular protein transport causes accumulation of neurotoxic proteins APP, Aβ and phosphorylated Tau, dysproteostasis, unfolded protein response, and apoptosis, which ultimately manifests in progressive cognitive decline, similar to the pathognomonic signatures of familial and sporadic forms of Alzheimer´s disease...
May 3, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29724333/-not-being-recognised-in-the-fight-against-alzheimer-s-disease-a-non-sharable-pain
#19
REVIEW
Cyril Hazif-Thomas
The pain of not being recognised in the fight against Alzheimer's disease is a question of non-sharing rarely considered by medicine, but which is nevertheless a significant issue for the patient and carer. This anxiety relating to the fracture of the being emerges when being faced with the ordeal of Alzheimer's disease becomes a source of unfathomable helplessness. It is the question facing the caregiver with the arrival of the fateful stage of the non-recognition of the carer by the patient and the consequent lack of acknowledgement on the part of his or her family, and the non-sharing of his or her suffering which is not easily accepted by society...
May 2018: Soins. Gérontologie
https://www.readbyqxmd.com/read/29720226/increased-a20-e3-ubiquitin-ligase-interactions-in-bid-deficient-glia-attenuate-tlr3-and-tlr4-induced-inflammation
#20
Sinéad Kinsella, Michael Fichtner, Orla Watters, Hans-Georg König, Jochen H M Prehn
BACKGROUND: Chronic pro-inflammatory signaling propagates damage to neural tissue and affects the rate of disease progression. Increased activation of Toll-like receptors (TLRs), master regulators of the innate immune response, is implicated in the etiology of several neuropathologies including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. Previously, we identified that the Bcl-2 family protein BH3-interacting domain death agonist (Bid) potentiates the TLR4-NF-κB pro-inflammatory response in glia, and specifically characterized an interaction between Bid and TNF receptor associated factor 6 (TRAF6) in microglia in response to TLR4 activation...
May 2, 2018: Journal of Neuroinflammation
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