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Alzheimer' disease

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https://www.readbyqxmd.com/read/29782959/targeting-central-%C3%AE-2-receptors-ameliorates-streptozotocin-induced-neuroinflammation-via-inhibition-of-glycogen-synthase-kinase3-pathway-in-mice
#1
Nora O Abdel Rasheed, Nesrine S El-Sayed, Aiman S El-Khatib
Alzheimer's disease (AD) is portrayed by progressive cognitive decline and pathological deposition of amyloid plaques as well as neurofibrillary tangles. Most of AD cases are sporadic, resulting from overlap of various environmental and genetic factors. Intra-cerebroventricular injection of streptozotocin (STZ) leads to insulin resistance brain state accompanied by memory decline, oxidative stress, and neuro-degeneration which mimic the pathologies associated with sporadic Alzheimer's disease (SAD). In the current study, protective effects of formoterol in STZ-induced SAD were studied...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29782957/the-role-of-monoamines-in-the-development-of-alzheimer-s-disease-and-neuroprotective-effect-of-a-proline-rich-polypeptide
#2
Konstantin Yenkoyan, Katarine Fereshetyan, Senik Matinyan, Vergine Chavushyan, Michail Aghajanov
INTRODUCTION: We have analyzed the alterations in the brain monoaminergic system using the rat model of AD-like pathology. In addition, we have investigated potential neuroprotective effects of the hypothalamic proline-rich polypeptide (PRP-1). METHODS: Histochemical staining, HPLC, chemiluminescent and bioluminescence assays. RESULTS: The levels of monoamines in the target AD brain structures were found elevated, except serotonin, which was unaffected in both hippocampus and brainstem and decreased in frontal cortex...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29782955/loss-of-calretinin-and-parvalbumin-positive-interneurones-in-the-hippocampal-ca1-of-aged-alzheimer-s-disease-mice
#3
Fatima Zallo, Emanuela Gardenal, Alexei Verkhratsky, José Julio Rodríguez
Neuronal degeneration associated with Alzheimer's disease (AD), is linked to impaired calcium homeostasis and to changes in calcium-binding proteins (CBPs). The AD-related modification of neuronal CBPs remains controversial. Here we analyzed the presence and expression of calretinin (CR) and parvalbumin (PV) in the hippocampal CA1 neurones of 18 months old 3xTg-AD mice compared to non-Tg animals. We found a layer specific decrease in number of interneurones expressing CR and PV (by 33.7% and 52%, respectively)...
May 18, 2018: Neuroscience Letters
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
#4
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
#5
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
#6
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/29782874/are-alzheimer-s-disease-and-other-neurodegenerative-disorders-caused-by-impaired-signalling-of-insulin-and-other-hormones
#7
EDITORIAL
Christian Hölscher, Fernanda G De Felice, Nigel Greig, Sergio T Ferreira
No abstract text is available yet for this article.
May 18, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29782836/dancing-with-the-diva-hsp90-client-interactions
#8
REVIEW
Martina Radli, Stefan G D Rüdiger
The molecular chaperone Hsp90 is involved in the folding, maturation and degradation of a large number structurally and sequentially unrelated clients, often connected to serious diseases. Elucidating the principles of how Hsp90 recognises this large variety of substrates is essential for comprehending the mechanism of this chaperone machinery, as well as it is a prerequisite for the design of client specific drugs targeting Hsp90. Here, we discuss the recent progress in understanding the substrate recognition principles of Hsp90 and its implications for the role of Hsp90 in the lifecycle of (signalling) molecules...
May 18, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29782833/insights-into-stabilizing-forces-in-amyloid-fibrils-of-differing-sizes-from-polarizable-molecular-dynamics-simulations
#9
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/29782824/apoe-%C3%AE%C2%B54-associates-with-hippocampal-volume-learning-and-memory-across-the-spectrum-of-alzheimer-s-disease-and-dementia-with-lewy-bodies
#10
Usman Saeed, Saira S Mirza, Bradley J MacIntosh, Nathan Herrmann, Julia Keith, Joel Ramirez, Sean M Nestor, Qinggang Yu, Jo Knight, Walter Swardfager, Steven G Potkin, Ekaterina Rogaeva, Peter St George-Hyslop, Sandra E Black, Mario Masellis
INTRODUCTION: Although the apolipoprotein E ε4-allele (APOE-ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored. METHODS: We studied 298 patients (AD = 250, DLB = 48; 38 autopsy confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE-ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis...
May 18, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
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
#11
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
#12
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
#13
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/29782389/development-of-a-novel-self-administered-cognitive-assessment-tool-and-normative-data-for-older-adults
#14
Raphael J Monsch, Amélie C Burckhardt, Manfred Berres, Alessandra E Thomann, Michael M Ehrensperger, Luzius A Steiner, Nicolai Goettel
BACKGROUND: Preexisting cognitive impairment in surgical patients is one of the leading risk factors for adverse cognitive outcomes such as postoperative delirium and postoperative cognitive dysfunction. We developed a self-administered tablet computer application intended to assess the individual risk for adverse postoperative cognitive outcomes. This cross-sectional study aimed to establish normative data for the tool. MATERIALS AND METHODS: Healthy volunteers aged 65 years and above were administered the Mini-Mental State Examination, Geriatric Depression Scale, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery to assess cognitive health...
May 18, 2018: Journal of Neurosurgical Anesthesiology
https://www.readbyqxmd.com/read/29782326/increased-albumin-oxidation-in-cerebrospinal-fluid-and-plasma-from-alzheimer-s-disease-patients
#15
Montserrat Costa, Raquel Horrillo, Ana María Ortiz, Alba Pérez, Anna Mestre, Agustín Ruiz, Mercè Boada, Salvador Grancha
BACKGROUND: Oxidative stress in the brain and peripheral systems is considered a major player in Alzheimer's disease (AD). Albumin is the main transporter and the main extracellular antioxidant in the human body. OBJECTIVE: Here we explore for the first time the oxidation status of cerebrospinal fluid (CSF) and plasma albumin in AD in comparison to healthy subjects. METHODS: Plasma and CSF samples were obtained from mild-moderate AD patients and control healthy age-matched donors...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782325/early-emotional-attention-is-impacted-in-alzheimer-s-disease-an-eye-tracking-study
#16
Jessica Bourgin, Nathalie Guyader, Alan Chauvin, Alexandra Juphard, Mathilde Sauvée, Olivier Moreaud, Laetitia Silvert, Pascal Hot
Emotional deficits have been repetitively reported in Alzheimer's disease (AD) without clearly identifying how emotional processing is impaired in this pathology. This paper describes an investigation of early emotional processing, as measured by the effects of emotional visual stimuli on a saccadic task involving both pro (PS) and anti (AS) saccades. Sixteen patients with AD and 25 age-matched healthy controls were eye-tracked while they had to quickly move their gaze toward a positive, negative, or neutral image presented on a computer screen (in the PS condition) or away from the image (in the AS condition)...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782324/meta-analysis-of-the-association-between-variants-in-abca7-and-alzheimer-s-disease
#17
Fang-Chen Ma, Hui-Fu Wang, Xi-Peng Cao, Chen-Chen Tan, Lan Tan, Jin-Tai Yu
The ATP-binding cassette transporter A7 (ABCA7) was identified as a known risk factor for Alzheimer's disease (AD). However, the relation between ABCA7 and AD was still inconsistent across these studies. Here, our meta-analysis aimed at confirming the association of ABCA7 with AD. Finally, 16 case-control studies (63747 versus 85833) were retrieved from PubMed and other databases. Three common loci were confirmed to increase the risk of AD (rs3764650: OR = 1.20, 95% CI = 1.16-1.24; rs3752246: OR = 1...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782323/role-of-blood-brain-barrier-in-alzheimer-s-disease
#18
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/29782322/inhibition-of-histone-acetylation-by-anp32a-induces-memory-deficits
#19
Gao-Shang Chai, Qiong Feng, Rong-Hong Ma, Xiao-Hang Qian, Dan-Ju Luo, Zhi-Hao Wang, Yu Hu, Dong-Sheng Sun, Jun-Fei Zhang, Xiao Li, Xiao-Guang Li, Dan Ke, Jian-Zhi Wang, Xi-Fei Yang, Gong-Ping Liu
There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782321/pyk2-is-a-novel-tau-tyrosine-kinase-that-is-regulated-by-the-tyrosine-kinase-fyn
#20
Chuanzhou Li, Jürgen Götz
The protein tyrosine kinase Pyk2 is encoded by PTK2B, a novel Alzheimer's disease (AD) susceptibility variant, with the PTK2B risk allele being associated with increased mRNA levels, suggestive of increased Pyk2 levels. However, the role of Pyk2, a member of the focal adhesion kinase (FAK) family, in AD pathology and its regulation are largely unknown. To address this, we generated mice with neuronal expression of human Pyk2. Because we had previously reported an association of Pyk2 and hyperphosphorylated tau (a hallmark feature of AD) in human tau transgenic pR5 mice, we also generated Pyk2/tau double-transgenic mice, which exhibit increased tyrosine phosphorylation and accumulation of tau...
May 16, 2018: Journal of Alzheimer's Disease: JAD
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