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https://www.readbyqxmd.com/read/29786737/anti-amyloidogenic-properties-of-an-ethyl-acetate-fraction-from-actinidia-arguta-in-a%C3%AE-1-42-induced-icr-mice
#1
Jeong Su Ha, Jong Min Kim, Seon Kyeong Park, Jin Yong Kang, Du Sang Lee, Uk Lee, Dae-Ok Kim, Sung-Gil Choi, Ho Jin Heo
This study aimed to investigate the ameliorating effect of an ethyl acetate fraction from the fruit Actinidia arguta (EFAA) on amyloid beta (Aβ)-induced neurotoxicity and cognitive deficits in ICR mice. EFAA showed potent protective effects against Aβ-induced neurotoxicity through 2',7'-dichlorofluorescein diacetate (DCF-DA), 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release into the assay medium. EFAA treatment reduced the intracellular ROS level and lactate dehydrogenase (LDH) release in the mitochondria, and increased cell viability in Aβ-induced neuroblastoma MC-IXC cells...
May 22, 2018: Food & Function
https://www.readbyqxmd.com/read/29784049/identification-and-therapeutic-modulation-of-a-pro-inflammatory-subset-of-disease-associated-microglia-in-alzheimer-s-disease
#2
Srikant Rangaraju, Eric B Dammer, Syed Ali Raza, Priyadharshini Rathakrishnan, Hailian Xiao, Tianwen Gao, Duc M Duong, Michael W Pennington, James J Lah, Nicholas T Seyfried, Allan I Levey
BACKGROUND: Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer's disease (AD). An understanding of heterogeneity within DAM and their key regulators may guide pre-clinical experimentation and drug discovery. METHODS: Weighted co-expression network analysis (WGCNA) was applied to existing microglial transcriptomic datasets from neuroinflammatory and neurodegenerative disease mouse models to identify modules of highly co-expressed genes...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29782912/in-vitro-protective-activity-of-south-australian-marine-sponge-and-macroalgae-extracts-against-amyloid-beta-a%C3%AE-1-42-induced-neurotoxicity-in-pc-12-cells
#3
Mousa Alghazwi, Scott Smid, Wei Zhang
South Australia is a biodiversity hotspot of marine sponges and macroalgae. This study aimed to evaluate the potential neuroprotective activity of extracts from these two marine sources by reducing the toxicity of human amyloid beta Aβ1-42 in a cell model assay using PC-12 cells. A total of 92 extracts (43, 13, 16, and 20 extracts from sponge of 8 orders and 17 families, green algae of 3 orders and 4 families, brown algae of 6 orders and 8 families, and red algae of 5 orders and 10 families, respectively) were initially screened at three different concentrations (0...
May 18, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29782911/estrogen-deficiency-exacerbates-a%C3%AE-induced-memory-impairment-through-enhancement-of-neuroinflammation-amylodogenesis-and-nf-%C3%A4-b-activation-in-ovariectomized-mice
#4
Jaesuk Yun, In Jun Yeo, Chul Ju Hwang, Dong-Young Choi, Hyung-Sik Im, Ji Youg Kim, Won Rak Choi, Myung Hee Jung, Sang-Bae Han, Jin Tae Hong
Estrogen is well known to have a preventative effect in Alzheimer's disease (AD) pathology. Several studies have demonstrated that nuclear factor kappa-B (NF-ĸB) can contribute to the effects of estrogen on the development of AD. We investigated whether NF-ĸB affects amyloid-beta (Aβ)-induced memory impairment in an estrogen-lacking condition. In the present study, nine-week-old Institute cancer research (ICR) mice were ovariectomized to block estrogen stimulation. Ten weeks after the ovariectomization, mice were administered with Aβ (300 pmol) via intracerebroventricular (ICV) infusion for 2 weeks...
May 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29782905/pathology-of-nnos-expressing-gabaergic-neurons-in-mouse-model-of-alzheimer-s-disease
#5
Seungho Choi, Je-Seong Won, Steven L Carroll, Balasubramaniam Annamalai, Inderjit Singh, Avtar K Singh
Alzheimer's disease (AD) is the most common form of dementia that is often accompanied by mood and emotional disturbances and seizures. There is growing body of evidence that neurons expressing γ-aminobutyric acid (GABA) play an important role in regulation of cognition, mood, and emotion as well as seizure susceptibility, but participation of GABAergic neuronal pathology in Alzheimer's disease (AD) is not understood well at present. Here, we report that transgenic mice expressing human amyloid precursor protein Swedish-Deutch-Iowa mutant (APPSweDI ) exhibit early loss of neurons expressing GAD67, a GABA synthesizing enzyme, in advance to the loss of pyramidal neurons in hippocampal CA1 region...
May 18, 2018: Neuroscience
https://www.readbyqxmd.com/read/29782833/insights-into-stabilizing-forces-in-amyloid-fibrils-of-differing-sizes-from-polarizable-molecular-dynamics-simulations
#6
Darcy S Davidson, Anne M Brown, Justin A Lemkul
Pathological aggregation of amyloid-forming proteins is a hallmark of a number of human diseases, including Alzheimer's, type 2 diabetes, Parkinson's, and more. Despite having very different primary amino acid sequences, these amyloid proteins form similar supramolecular, fibril structures that are highly resilient to physical and chemical denaturation. To better understand the structural stability of disease-related amyloids and to gain a greater understanding of factors that stabilize functional amyloid assemblies, insights into tertiary and quaternary interactions are needed...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782798/regulatory-activities-of-dopamine-and-its-derivatives-towards-metal-free-and-metal-induced-amyloid-%C3%AE-aggregation-oxidative-stress-and-inflammation-in-alzheimer-s-disease
#7
Eunju Nam, Jeffrey S Derrick, Seunghee Lee, Juhye Kang, Jiyeon Han, Shin Jung C Lee, Su Wol Chung, Mi Hee Lim
A catecholamine neurotransmitter, dopamine (DA), is suggested to be linked to the pathology of dementia; however, the involvement of DA and its structural analogues in the pathogenesis of Alzheimer's disease (AD), the most common form of dementia, composed of multiple pathogenic factors has not been clear. Herein, we report that DA and its rationally designed structural derivatives (1-6) based on DA's oxidative transformation are able to modulate multiple pathological elements found in AD [ i.e., metal ions, metal-free amyloid-β (Aβ), metal-bound Aβ (metal-Aβ), and reactive oxygen species (ROS)], with demonstration of detailed molecular-level mechanisms...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782794/peptides-peptidomimetics-and-carbohydrate-peptide-conjugates-as-amyloidogenic-aggregation-inhibitors-for-alzheimer-s-disease
#8
Philip Ryan, Bhautikkumar Patel, Vivek Makwana, Hemant Jadhav, Milton John Kiefel, Andrew Davey, Tristan Reekie, Santosh Rudrawar, Michael Kassiou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted towards the aggregation of the peptide tau as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782502/a-monoclonal-antibody-targeting-amyloid-%C3%AE-a%C3%AE-restores-complement-factor-i-bioactivity-potential-implications-in-age-related-macular-degeneration-and-alzheimer-s-disease
#9
Kameran Lashkari, Gianna Teague, Hong Chen, Yong-Qing Lin, Sanjay Kumar, Megan M McLaughlin, Francisco J López
Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies...
2018: PloS One
https://www.readbyqxmd.com/read/29782323/role-of-blood-brain-barrier-in-alzheimer-s-disease
#10
Zhiyou Cai, Pei-Feng Qiao, Cheng-Qun Wan, Min Cai, Nan-Kai Zhou, Qin Li
The blood-brain barrier (BBB) is involved in the pathogenesis of Alzheimer's disease (AD). BBB is a highly selective semipermeable structural and chemical barrier which ensures a stable internal environment of the brain and prevents foreign objects invading the brain tissue. BBB dysfunction induces the failure of Aβ transport from brain to the peripheral circulation across the BBB. Especially, decreased levels of LRP-1 (low density lipoprotein receptor-related protein 1) and increased levels of RAGE (receptor for advanced glycation endproducts) at the BBB can cause the failure of Aβ transport...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782318/amyloid-accumulation-and-cognitive-decline-in-clinically-normal-older-individuals-implications-for-aging-and-early-alzheimer-s-disease
#11
Elizabeth C Mormino, Kathryn V Papp
 The aberrant accumulation of the amyloid protein is a critical and early event in the Alzheimer's disease (AD) cascade. Given the early involvement of this pathological process, it is not surprising that many clinically normal (CN) older individuals demonstrate evidence of abnormal Aβ at postmortem examination and in vivo using either CSF or PET imaging. Converging evidence across multiple research groups suggests that the presence of abnormal Aβ among CN individuals is associated with elevated risk of future clinical impairment and cognitive decline...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782313/kainic-acid-impairs-the-memory-behavior-of-app23-mice-by-increasing-brain-amyloid-load-through-a-tumor-necrosis-factor-%C3%AE-dependent-mechanism
#12
Yang Ruan, Shi-Jie Guo, Xu Wang, Dong Dong, Dong-Hui Shen, Jie Zhu, Xiang-Yu Zheng
Kainic acid (KA) was recently identified as an epileptogenic and neuroexcitotoxic agent that is responsible for inducing learning and memory deficits in various neurodegenerative diseases, such as Alzheimer's disease (AD). However, the mechanism by which KA acts upon AD remains unclear. To this end, we presently investigated the roles of KA in processing amyloid-β protein precursor (AβPP) and amyloid-β protein (Aβ) loads during the course of AD development and progression. Specifically, KA treatment clearly caused the upregulation of tumor necrosis factor α (TNF-α) via activation of the PI3-K/AKT, ERK1/2, and p65 pathways in glial cells...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29781021/dynamical-crossover-of-water-confined-within-the-amphiphilic-nanocores-of-aggregated-amyloid-%C3%AE-peptides
#13
Prabir Khatua, Sanjoy Bandyopadhyay
It is believed that the self-assembly of amyloid beta (Aβ) peptides in the brain is the cause of Alzheimer's disease. Atomistic molecular dynamics simulations of aqueous solutions of Aβ protofilaments of different sizes at room temperature have been carried out to explore the dynamic properties of water confined within the core and at the exterior surface of the protofilaments. Attempts have been made to understand how the non-uniform distortion of the protofilaments associated with their structural crossover influences the diffusivity and the hydrogen bonding environment of the confined water molecules...
May 21, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29780875/amyloid-%C3%AE-peptides-are-differentially-vulnerable-to-preanalytical-surface-exposure-an-effect-incompletely-mitigated-by-the-use-of-ratios
#14
Jamie Toombs, Martha S Foiani, Henrietta Wellington, Ross W Paterson, Charles Arber, Amanda Heslegrave, Michael P Lunn, Jonathan M Schott, Selina Wray, Henrik Zetterberg
Introduction: We tested the hypothesis that the amyloid β (Aβ) peptide ratios are more stable than Aβ42 alone when biofluids are exposed to two preanalytical conditions known to modify measurable Aβ concentration. Methods: Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were exposed to a series of volumes and polypropylene surfaces. Aβ42 , Aβ40 , and Aβ38 peptide concentrations were measured using a multiplexed electrochemiluminescence immunoassay...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780869/cross-sectional-and-longitudinal-atrophy-is-preferentially-associated-with-tau-rather-than-amyloid-%C3%AE-positron-emission-tomography-pathology
#15
Brian A Gordon, Austin McCullough, Shruti Mishra, Tyler M Blazey, Yi Su, John Christensen, Aylin Dincer, Kelley Jackson, Russ C Hornbeck, John C Morris, Beau M Ances, Tammie L S Benzinger
Introduction: Structural magnetic resonance imaging is a marker of gray matter health and decline that is sensitive to impaired cognition and Alzheimer's disease pathology. Prior work has shown that both amyloid β (Aβ) and tau biomarkers are related to cortical thinning, but it is unclear what unique influences they have on the brain. Methods: Aβ pathology was measured with [18 F] AV-45 (florbetapir) positron emission tomography (PET) and tau was assessed with [18 F] AV-1451 (flortaucipir) PET in a population of 178 older adults, of which 123 had longitudinal magnetic resonance imaging assessments (average of 5...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29780861/the-relationship-between-recall-of-recently-versus-remotely-encoded-famous-faces-and-amyloidosis-in-clinically-normal-older-adults
#16
Irina Orlovsky, Willem Huijbers, Bernard J Hanseeuw, Elizabeth C Mormino, Trey Hedden, Rachel F Buckley, Molly LaPoint, Jennifer S Rabin, Dorene M Rentz, Keith A Johnson, Reisa A Sperling, Kathryn V Papp
Introduction: Alzheimer's disease (AD) patients exhibit temporally graded memory loss with remote memories remaining more intact than recent memories. It is unclear whether this temporal pattern is observable in clinically normal adults with amyloid pathology (i.e. preclinical AD). Methods: Participants were asked to recall the names of famous figures most prominent recently (famous after 1990) and remotely (famous from 1960-1980) and were provided with a phonemic cue to ensure that memory failure was not purely due to verbal retrieval weaknesses...
2018: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#17
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29777753/characterization-of-impaired-cerebrovascular-structure-in-app-ps1-mouse-brains
#18
Kee-Chan Ahn, Cameron R Learman, Gary L Dunbar, Panchanan Maiti, Won-Cheoul Jang, Hyeon-Cheol Cha, Mee-Sook Song
Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29777707/functional-analysis-of-juxta-and-intra-membrane-domains-of-murine-app-by-genome-editing-in-neuro2a-cells
#19
Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777699/cart-peptide-activates-the-nrf2-ho-1-antioxidant-pathway-and-protects-hippocampal-neurons-in-a-rat-model-of-alzheimer-s-disease
#20
Wenyu Jiao, Yongchen Wang, Linghong Kong, Tao Ou-Yang, Qing Meng, Qiang Fu, Zhenzhen Hu
The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0...
May 16, 2018: Biochemical and Biophysical Research Communications
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