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Amyloid-β

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https://www.readbyqxmd.com/read/29161719/palmitic-acid-curcumin-ester-facilitates-protection-of-neuroblastoma-against-oligomeric-a%C3%AE-40-insult
#1
Zhangyang Qi, Meihao Wu, Yun Fu, Tengfei Huang, Tingting Wang, Yanjie Sun, Zhibo Feng, Changzheng Li
BACKGROUND/AIMS: The generation of reactive oxygen species (ROS) caused by amyloid-β (Aβ) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aβ-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aβ may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aβ...
November 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29161341/distinct-spatiotemporal-accumulation-of-n-truncated-and-full-length-amyloid-%C3%AE-42-in-alzheimer-s-disease
#2
Mitsuru Shinohara, Shunsuke Koga, Takuya Konno, Jeremy Nix, Motoko Shinohara, Naoya Aoki, Pritam Das, Joseph E Parisi, Ronald C Petersen, Terrone L Rosenberry, Dennis W Dickson, Guojun Bu
Accumulation of amyloid-β peptides is a dominant feature in the pathogenesis of Alzheimer's disease; however, it is not clear how individual amyloid-β species accumulate and affect other neuropathological and clinical features in the disease. Thus, we compared the accumulation of N-terminally truncated amyloid-β and full-length amyloid-β, depending on disease stage as well as brain area, and determined how these amyloid-β species respectively correlate with clinicopathological features of Alzheimer's disease...
November 17, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29159265/characterizing-biomarker-features-of-cognitively-normal-individuals-with-ventriculomegaly
#3
Xiaofeng Li, Maowen Ba, Kok Pin Ng, Sulantha Mathotaarachchi, Tharick A Pascoal, Pedro Rosa-Neto, Serge Gauthier
Introduction: The clinical significance of ventriculomegaly in cognitively normal elderly individuals remains unclear. Methods: We selected cognitively normal individuals (n = 425) from the Alzheimer's Disease Neuroimaging Initiative database and calculated Evans index (EI) based on the ratio of the frontal horn and skull diameter. We defined ventriculomegaly as EI ≥ 0.30, and the participants were stratified into EI ≥ 0.30 group and EI < 0.30 group...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29158778/helicobacter-pylori-and-gut-microbiota-in-multiple-sclerosis-versus-alzheimer-s-disease-10-pitfalls-of-microbiome-studies
#4
Ah-Mee Park, Seiichi Omura, Mitsugu Fujita, Fumitaka Sato, Ikuo Tsunoda
Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of "good bacteria" such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while "bad bacteria" such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer's disease (AD)...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/29158413/amyloid-polymorphisms-constitute-distinct-clouds-of-conformational-variants-in-different-etiological-subtypes-of-alzheimer-s-disease
#5
Jay Rasmussen, Jasmin Mahler, Natalie Beschorner, Stephan A Kaeser, Lisa M Häsler, Frank Baumann, Sofie Nyström, Erik Portelius, Kaj Blennow, Tammaryn Lashley, Nick C Fox, Diego Sepulveda-Falla, Markus Glatzel, Adrian L Oblak, Bernardino Ghetti, K Peter R Nilsson, Per Hammarström, Matthias Staufenbiel, Lary C Walker, Mathias Jucker
The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-β peptide (Aβ) has been shown to adopt distinct structural conformations with different biological activities, we asked whether Aβ can assume structurally and functionally distinct conformations within the brain...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29158112/subtle-behavioral-changes-and-increased-prefrontal-hippocampal-network-synchronicity-in-app-nl-g-f-mice-before-prominent-plaque-deposition
#6
Amira Latif Hernandez, Disha Shah, Kathleen Craessaerts, Takaomi Saido, Takashi Saito, Bart De Strooper, Annemie Van der Linden, Rudi D'Hooge
Amyloid-β (Aβ) peptides occur in the brains of patients with Alzheimer's disease (AD), but their role in functional impairment is still debated. High levels of APP and APP fragments in mice that overexpress APP might confound their use in preclinical research. We examined the occurrence of behavioral, cognitive and neuroimaging changes in APP(NL-G-F) knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression. Female APP(NL-G-F) mice (carrying Swedish, Iberian and Arctic APP mutations) were compared to APP(NL) mice (APP Swedish) at 3, 7 and 10 months...
November 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29155576/chronic-arsenic-exposure-increases-a%C3%AE-1-42-production-and-rage-expression-in-rat-brain
#7
Sandra Aurora Niño, Guadalupe Martel-Gallegos, Adriana Castro-Zavala, Benita Ortega-Berlanga, Juan Manuel Delgado, Hector Hernandez-Mendoza, E Romero-Guzman, Judith Rios-Lugo, Sergio Rosales-Mendoza, María Esther Jiménez-Capdeville, Sergio Zarazua
Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At cellular level, arsenic toxicity involves increased generation of reactive species that induce severe cellular alterations such as DNA fragmentation, apoptosis and lipid peroxidation. It has been proposed that arsenic-associated neurodegeneration could evolve to Alzheimer disease in later life.1,2 In this study, the effects of chronic exposure to inorganic arsenic (3 ppm by drinking water) in Wistar rats on the production and elimination of Amyloid-β (Aβ) were evaluated...
November 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29154879/perillyl-alcohol-alleviates-amyloid-%C3%AE-peptides-induced-mitochondrial-dysfunction-and-cytotoxicity-in-sh-sy5y-cells
#8
Mohammad Faraz Zafeer, Fakiha Firdaus, Faraz Ahmad, Rizwan Ullah, Ehraz Anis, Mohd Waseem, Asif Ali, Mohammad Mobarak Hossain
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia in elderly ( >65years of age). Excessive extra cellular deposits of amyloid beta (Aβ) are a pathological feature of AD. Aβ can cause cell death through oxidative damage; recent studies have implicated opening of mPTP as a detrimental event in AD-related mitochondrial dysfunctions. Over the past few years, natural compounds with antioxidant properties have shown promise for intervention in AD.
November 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29154286/clinic-based-validation-of-cerebrospinal-fluid-biomarkers-with-florbetapir-pet-for-diagnosis-of-dementia
#9
Ignacio Álvarez, Miquel Aguilar, Jose Manuel González, Montse Ysamat, Carles Lorenzo-Bosquet, Alvaro Alonso, Juan Pablo Tartari, Silvia Romero, Monica Diez-Fairen, Maria Carcel, Francisco Pujalte, Pau Pastor
BACKGROUND: Cerebrospinal fluid (CSF) biomarker studies have shown variable accuracy for diagnosis of Alzheimer's disease (AD); therefore, internal validation is recommended. OBJECTIVE: To investigate the correlation between CSF biomarkers and cerebral 18-Florbetapir positron emission tomography (Amyloid-PET) and calculate their sensitivity and specificity to obtain the optimal clinical cut-off points to diagnose the etiology of cognitive impairment. METHODS: We performed Amyloid-PET scans and CSF biomarker levels analyses in 68 subjects (50 with mild cognitive impairment, 11 with AD dementia, and 7 with non-AD dementia)...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154278/effects-of-physical-exercise-on-alzheimer-s-disease-biomarkers-a-systematic-review-of-intervention-studies
#10
Kristian Steen Frederiksen, Le Gjerum, Gunhild Waldemar, Steen Gregers Hasselbalch
Physical exercise may be an important adjunct to pharmacological treatment of Alzheimer's disease (AD). Animal studies indicate that exercise may be disease modifying through several mechanisms including reduction of AD pathology. We carried out a systematic review of intervention studies of physical exercise with hippocampal volume (on MRI), amyloid-β, total tau, phosphorylated tau in cerebrospinal fluid (CSF), 18F-FDG-PET or amyloid PET as outcome measures in healthy subjects, patients with subjective memory complaints, mild cognitive impairment, or AD...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154275/association-of-cerebrospinal-fluid-csf-insulin-with-cognitive-performance-and-csf-biomarkers-of-alzheimer-s-disease
#11
Stefan L C Geijselaers, Pauline Aalten, Inez H G B Ramakers, Peter Paul De Deyn, Annemieke C Heijboer, Huiberdina L Koek, Marcel G M OldeRikkert, Janne M Papma, Fransje E Reesink, Lieke L Smits, Coen D A Stehouwer, Charlotte E Teunissen, Frans R J Verhey, Wiesje M van der Flier, Geert Jan Biessels
BACKGROUND: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD). OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype. METHODS: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154274/cognitive-decline-in-preclinical-alzheimer-s-disease-amyloid-beta-versus-tauopathy
#12
Colin M Huber, Connor Yee, Taylor May, Apoorva Dhanala, Cassie S Mitchell
 We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). "High" levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154270/ubisol-q10-a-nanomicellar-water-soluble-formulation-of-coq10-treatment-inhibits-alzheimer-type-behavioral-and-pathological-symptoms-in-a-double-transgenic%C3%A2-mouse%C3%A2-tgapeswe-%C3%A2-psen1de9-model-of-alzheimer-s-disease
#13
Krithika Muthukumaran, Annie Kanwar, Caleb Vegh, Alexandra Marginean, Austin Elliott, Nicholas Guilbeault, Alexander Badour, Marianna Sikorska, Jerome Cohen, Siyaram Pandey
 Alzheimer's disease (AD) is one of the most common neurodegenerative pathologies for which there are no effective therapies to halt disease progression. Given the increase in the incidence of this disorder, there is an urgent need for pharmacological intervention. Unfortunately, recent clinical trials produced disappointing results. Molecular mechanisms of AD are converging on the notion that mitochondrial dysfunction, oxidative stress, and accumulation of dysfunctional proteins are involved in AD pathology...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29152258/in-vitro-screening-of-neuroprotective-activity-of-indian-medicinal-plant-withania-somnifera
#14
Manjeet Singh, Charles Ramassamy
Canine cognitive dysfunction (CCD) is an age-dependent neurodegenerative condition characterised by changes in decline in learning and memory patterns. The neurodegenerative features of CCD in ageing dogs and cats are similar to human ageing and Alzheimer's disease (AD). Discovering neuroprotective disease-modifying therapies against CCD and AD is a major challenge. Strong evidence supports the role of amyloid β peptide deposition and oxidative stress in the pathophysiology of CCD and AD. In both the human and canine brain, oxidative damage progressively increases with age...
2017: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29149834/cystatin-c-in-cerebrovascular-disorders
#15
Yaru Zhang, Li Sun
Cystatin C (CysC), a cysteine protease inhibitor, has been widely proven to be a highly sensitive biomarker to predict the kidney function. The similarity of the renal and cerebral small vessels has awakened a surge of studies suggesting that CysC plays a key role in various cerebrovascular disorders. This review focuses on four major mechanisms of CysC in a variety of cerebrovascular diseases. (1)The property of the CysC Leu-68-Gln (L68Q) variant to aggregate and the property of the wild type CysC protein to co-aggregate with Amyloid-β (Aβ); (2)The disruption of equilibrium between CysC and related cysteine proteases; (3)The function of CysC as an inflammatory inducing factor; (4)The ability of CysC to induce autophagy...
November 15, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/29148236/emerging-roles-of-er-stress-in-the-aetiology-and-pathogenesis-of-alzheimer-s-disease
#16
REVIEW
Yannis Gerakis, Claudio Hetz
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phophorylated Tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network is a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the Unfolded Protein Response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29143372/a-critical-role-of-trpm2-channel-in-a%C3%AE-42-induced-microglial-activation-and-generation-of-tumor-necrosis-factor-%C3%AE
#17
Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin-Hua Jiang
Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD...
November 16, 2017: Glia
https://www.readbyqxmd.com/read/29142106/soluble-a%C3%AE-aggregates-can-inhibit-prion-propagation
#18
Claire J Sarell, Emma Quarterman, Daniel C-M Yip, Cassandra Terry, Andrew J Nicoll, Jonathan D F Wadsworth, Mark A Farrow, Dominic M Walsh, John Collinge
Mammalian prions cause lethal neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD) and consist of multi-chain assemblies of misfolded cellular prion protein (PrP(C)). Ligands that bind to PrP(C) can inhibit prion propagation and neurotoxicity. Extensive prior work established that certain soluble assemblies of the Alzheimer's disease (AD)-associated amyloid β-protein (Aβ) can tightly bind to PrP(C), and that this interaction may be relevant to their toxicity in AD. Here, we investigated whether such soluble Aβ assemblies might, conversely, have an inhibitory effect on prion propagation...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29140083/a-critical-role-of-ser26-hydrogen-bonding-in-a%C3%AE-42-assembly-and-toxicity
#19
Robin Roychaudhuri, Tien-Phat V Huynh, Taylor R Whitaker, Elisabeth Hodara, Margaret M Condron, David B Teplow
Amyloid β-protein (Aβ) assembly is a seminal process in Alzheimer's disease. Elucidating the mechanistic features of this process is thought to be vital for the design and targeting of therapeutic agents. Com-putational studies of the most pathologic form of Aβ, the 42-residue Aβ42 peptide, have suggested that hydrogen bonding involving Ser 26 may be particularly important in organizing a monomer folding nucleus and in subse-quent peptide assembly. To study this question, we ex-perimentally determined structure-activity relationships among Aβ42 peptides in which Ser 26 was replaced with Gly, Ala, α-aminobutryic acid (Abu), or Cys...
November 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29138750/markers-of-alzheimer-s-disease-in-primary-visual-cortex-in-normal-aging-in-mice
#20
Luis Fernando Hernández-Zimbrón, Montserrat Perez-Hernández, Abigail Torres-Romero, Elisa Gorostieta-Salas, Roberto Gonzalez-Salinas, Rosario Gulias-Cañizo, Hugo Quiroz-Mercado, Edgar Zenteno
Aging is the principal risk factor for the development of Alzheimer's disease (AD). The hallmarks of AD are accumulation of the amyloid-β peptide 1-42 (Aβ42) and abnormal hyperphosphorylation of Tau (p-Tau) protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood...
2017: BioMed Research International
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