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Amyloid beta tau protein

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https://www.readbyqxmd.com/read/29626319/clearance-of-amyloid-beta-and-tau-in-alzheimer-s-disease-from-mechanisms-to-therapy
#1
REVIEW
Shu-Hui Xin, Lin Tan, Xipeng Cao, Jin-Tai Yu, Lan Tan
Alzheimer's disease (AD) is the most common neurodegenerative disease. Pathological proteins of AD mainly contain amyloid-beta (Aβ) and tau. Their deposition will lead to neuron damage by a series of pathways, and then induce memory and cognitive impairment. Thus, it is pivotal to understand the clearance pathways of Aβ and tau in order to delay or even halt AD. Aβ clearance mechanisms include ubiquitin-proteasome system, autophagy-lysosome, proteases, microglial phagocytosis, and transport from the brain to the blood via the blood-brain barrier (BBB), arachnoid villi and blood-CSF barrier, which can be named blood circulatory clearance...
April 7, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29611103/evidence-for-compromised-insulin-signaling-and-neuronal-vulnerability-in-experimental-model-of-sporadic-alzheimer-s-disease
#2
Smriti Gupta, Kamalendra Yadav, Shrikant S Mantri, Nitin K Singhal, Subramaniam Ganesh, Rajat Sandhir
Evidence from animal studies categorizes sporadic Alzheimer's disease (sAD) as a metabolic syndrome with accompanying cognitive deficits. Given that glial cells act as "silent partners" to neurons by providing trophic support and defense, the present study investigated the role of glia in sAD pathology. A streptozotocin (STZ)-induced glial-neuronal co-culture model of sAD was used to study the metabolic status of the two cell types. Real time RT-PCR and Western blotting results indicated that amyloid precursor protein (APP) and β-secretase (BACE1) were highly expressed in co-cultured neurons than in monocultures...
April 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29582495/targeting-alzheimer-s-disease-with-gene-and-cell-therapies
#3
REVIEW
Raúl Loera-Valencia, Antonio Piras, Muhammad Al Mustafa Ismail, Shaffi Manchanda, Helga Eyjolfsdottir, Takaomi C Saido, Jan Johansson, Maria Eriksdotter, Bengt Winblad, Per Nilsson
Alzheimer’ s disease (AD) causes dementia in both young and old people affecting more than 40 million people worldwide. The two neuropathological hallmarks of the disease, amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of protein tau are considered the major contributors to the disease. However, a more complete picture reveals significant neurodegeneration and decreased cell survival, neuroinflammation, changes in protein homeostasis and alterations in lipid and cholesterol metabolism...
March 26, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29562530/cerebrospinal-fluid-biomarkers-for-early-and-differential-alzheimer-s-disease-diagnosis
#4
Maria Bjerke, Sebastiaan Engelborghs
An accurate and early diagnosis of Alzheimer's disease (AD) is important to select optimal patient care and is critical in current clinical trials targeting core AD neuropathological features. The past decades, much progress has been made in the development and validation of cerebrospinal fluid (CSF) biomarkers for the biochemical diagnosis of AD, including standardization and harmonization of (pre-) analytical procedures. This has resulted in three core CSF biomarkers for AD diagnostics, namely the 42 amino acid long amyloid-beta peptide (Aβ1-42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29559905/molecular-mechanisms-for-herpes-simplex-virus-type-1-pathogenesis-in-alzheimer-s-disease
#5
REVIEW
Steven A Harris, Elizabeth A Harris
This review focuses on research in the areas of epidemiology, neuropathology, molecular biology and genetics that implicates herpes simplex virus type 1 (HSV-1) as a causative agent in the pathogenesis of sporadic Alzheimer's disease (AD). Molecular mechanisms whereby HSV-1 induces AD-related pathophysiology and pathology, including neuronal production and accumulation of amyloid beta (Aβ), hyperphosphorylation of tau proteins, dysregulation of calcium homeostasis, and impaired autophagy, are discussed. HSV-1 causes additional AD pathologies through mechanisms that promote neuroinflammation, oxidative stress, mitochondrial damage, synaptic dysfunction, and neuronal apoptosis...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29559004/diagnostic-value-of-cerebrospinal-fluid-tau-neurofilament-and-progranulin-in-definite-frontotemporal-lobar-degeneration
#6
Joery Goossens, Maria Bjerke, Sara Van Mossevelde, Tobi Van den Bossche, Johan Goeman, Bart De Vil, Anne Sieben, Jean-Jacques Martin, Patrick Cras, Peter Paul De Deyn, Christine Van Broeckhoven, Julie van der Zee, Sebastiaan Engelborghs
BACKGROUND: We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD), as well as between FTLD pathological subtypes. METHODS: CSF levels of routine AD biomarkers (phosphorylated tau (p-tau181 ), total tau (t-tau), and amyloid-beta (Aβ)1-42 ) and neurofilament proteins, as well as progranulin levels in both CSF and serum were quantified in definite FTLD (n = 46), clinical AD (n = 45), and cognitively healthy controls (n = 20)...
March 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29558979/cerebrospinal-fluid-in-the-differential-diagnosis-of-alzheimer-s-disease-clinical-utility-of-an-extended-panel-of-biomarkers-in-a-specialist-cognitive-clinic
#7
Ross W Paterson, Catherine F Slattery, Teresa Poole, Jennifer M Nicholas, Nadia K Magdalinou, Jamie Toombs, Miles D Chapman, Michael P Lunn, Amanda J Heslegrave, Martha S Foiani, Philip S J Weston, Ashvini Keshavan, Jonathan D Rohrer, Martin N Rossor, Jason D Warren, Catherine J Mummery, Kaj Blennow, Nick C Fox, Henrik Zetterberg, Jonathan M Schott
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias. METHODS: We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls...
March 20, 2018: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29506051/gsk-3%C3%AE-mtorc1-couples-synaptogenesis-and-axonal-repair-to-reduce-hypoxia-ischemia-mediated-brain-injury-in-neonatal-rats
#8
Tao Xiong, Yi Qu, Huiqin Wang, Hongju Chen, Jianghu Zhu, Fengyan Zhao, Rong Zou, Li Zhang, Dezhi Mu
Glycogen synthase kinase 3 beta (GSK-3β) plays an important role in neurological outcomes after brain injury. However, its roles and mechanisms in hypoxia-ischemia (HI) are unclear. Activation of mTOR complex 1 (mTORC1) has been proven to induce the synthesis of proteins associated with regeneration. We hypothesized that GSK-3β inhibition could activate the mTORC1 signaling pathway, which may reduce axonal injury and induce synaptic protein synthesis and functional recovery of synapses after HI. By analyzing a P7 rat model of cerebral HI and an in vitro ischemic (oxygen glucose deprivation) model, we found that GSK-3β inhibitors (GSK-3β siRNA or lithium chloride) activated mTORC1 signaling, leading to increased expression of synaptic proteins, including synapsin 1, PSD95, and GluR1, and the microtubule-associated protein Tau and decreased expression of the axonal injury-associated protein amyloid precursor protein...
February 28, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29503090/stabilizing-the-retromer-complex-in-a-human-stem-cell-model-of-alzheimer-s-disease-reduces-tau-phosphorylation-independently-of-amyloid-precursor-protein
#9
Jessica E Young, Lauren K Fong, Harald Frankowski, Gregory A Petsko, Scott A Small, Lawrence S B Goldstein
Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29497399/tau-filaments-and-the-development-of-positron-emission-tomography-tracers
#10
REVIEW
Michel Goedert, Yoshiki Yamaguchi, Sushil K Mishra, Makoto Higuchi, Naruhiko Sahara
A pathological pathway leading from soluble, monomeric to insoluble, filamentous Tau, is believed to underlie human Tauopathies. Cases of frontotemporal dementia are caused by dominantly inherited mutations in MAPT , the Tau gene. They show that dysfunction of Tau protein is sufficient to cause neurodegeneration and dementia. Extrapolation to the more common sporadic Tauopathies leads one to conclude that the pathological pathway is central to the development of all cases of disease, even if there are multiple reasons for Tau assembly...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29490235/premature-hippocampus-dependent-memory-decline-in-middle-aged-females-of-a-genetic-rat-model-of-depression
#11
Patrick H Lim, Stephanie L Wert, Elif Tunc-Ozcan, Robert Marr, Adriana Ferreira, Eva E Redei
Aging and major depressive disorder are risk factors for dementia, including Alzheimer's Disease (AD), but the mechanism(s) linking depression and dementia are not known. Both AD and depression show greater prevalence in women. We began to investigate this connection using females of the genetic model of depression, the inbred Wistar Kyoto More Immobile (WMI) rat. These rats consistently display depression-like behavior compared to the genetically close control, the Wistar Kyoto Less Immobile (WLI) strain. Hippocampus-dependent contextual fear memory did not differ between young WLI and WMI females, but, by middle-age, female WMIs showed memory deficits compared to same age WLIs...
February 25, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29484335/shedding-light-on-tau-protein-aggregation-the-progress-in-developing-highly-selective-fluorophores
#12
Peter Verwilst, Hyeong Seok Kim, Soobin Kim, Chulhun Kang, Jong Seung Kim
Historically, in Alzheimer's disease research, a lot of attention has been paid to the development of highly selective fluorophores for beta amyloid plaques. With a shift in the understanding of the disease and the importance of a network of cross-talk interactions, the development of small-molecule fluorescent dyes with high selectivity for (hyperphosphorylated) tau protein aggregates in neurofibrillary tangles has been gaining increasing attention. Fluorescent dyes for the selective labelling of tau aggregates in histological AD brain sections have been described, spanning the entire visible range of the electromagnetic spectrum...
February 27, 2018: Chemical Society Reviews
https://www.readbyqxmd.com/read/29482817/elevated-tau-and-interleukin-6-concentrations-in-adults-with-obstructive-sleep-apnea
#13
Vida Motamedi, Rebekah Kanefsky, Panagiotis Matsangas, Sara Mithani, Andreas Jeromin, Matthew S Brock, Vincent Mysliwiec, Jessica Gill
Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas that result in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules and, along with amyloid beta (Aβ), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Aβ40, Aβ42, c-reactive protein (CRP), TNF-α, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n = 28), those with mild OSA (n = 22), and healthy controls (n = 24)...
March 2018: Sleep Medicine
https://www.readbyqxmd.com/read/29481840/selenium-selenoprotein-p-and-alzheimer-s-disease-is-there-a-link
#14
REVIEW
Nikolay Solovyev, Evgenii Drobyshev, Geir Bjørklund, Yaroslav Dubrovskii, Roman Lysiuk, Margaret P Rayman
The essential trace element, selenium (Se), is crucial to the brain but it may be potentially neurotoxic, depending on dosage and speciation; Se has been discussed for decades in relation to Alzheimer's disease (AD). Selenoprotein P (SELENOP) is a secreted heparin-binding glycoprotein which serves as the main Se transport protein in mammals. In vivo studies showed that this protein might have additional functions such as a contribution to redox regulation. The current review focuses on recent research on the possible role of SELENOP in AD pathology, based on model and human studies...
February 23, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29480194/development-of-a-high-sensitivity-method-for-the-measurement-of-human-nasal-a%C3%AE-42-tau-and-phosphorylated-tau
#15
Ziyi Liu, Naoko Kameshima, Toshifumi Nanjo, Akihiko Shiino, Tomoko Kato, Shino Shimizu, Takeshi Shimizu, Sachiko Tanaka, Katsuyuki Miura, Ikuo Tooyama
Cost-effective and feasible methods for early diagnosis of Alzheimer's disease (AD) are needed. We present two methods to measure AD-related biomarkers simultaneously from one nasal smear for the purpose of diagnosing AD. Japanese men and women aged 63-85 years old were recruited in 2015-2016 for this case-control study. A total of 25 AD cases and 25 controls (22 men and 28 women) participated in this research. Nasal smears were collected from the common nasal meatus, inferior concha, middle nasal meatus, and olfactory cleft, and the proteins in the samples were analyzed by two methods, which we named PGD (Pre-treatment with guanidine- n-Dodecyl-beta-D-maltoside solution) method 1 (PGD-I) and 2 (PGD-II)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29478590/the-genetic-landscape-of-alzheimer-disease
#16
Susana Carmona, John Hardy, Rita Guerreiro
Alzheimer disease (AD), a progressive and neurodegenerative disease, is the most common form of dementia with high incidence in elderly people. Neuropathologically the disease is defined by the combined presence of extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles of phosphorylated tau protein. Genetically, the first clues were provided by genetic linkage studies that led to the identification of APP, PSEN1, and PSEN2 mutations as the main causes of autosomal-dominant early-onset AD...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29462698/piper-sarmentosum-roxb-confers-neuroprotection-on-beta-amyloid-a%C3%AE-induced-microglia-mediated-neuroinflammation-and-attenuates-tau-hyperphosphorylation-in-sh-sy5y-cells
#17
Emilia Tze Ying Yeo, Kelly Wang Ling Wong, Mun Ling See, Ka Yan Wong, Sook Yee Gan, Elaine Wan Ling Chan
ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aβ)-induced microglia-mediated neurotoxicity...
February 17, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29447949/protective-effects-of-alpinae-oxyphyllae-fructus-extracts-on-lipopolysaccharide-induced-animal-model-of-alzheimer-s-disease
#18
Yunlong Wang, Mengshi Wang, Kaiyue Fan, Tongde Li, Tingxu Yan, Bo Wu, Kaishun Bi, Ying Jia
ETHNOPHARMACOLOGICAL RELEVANCE: Alpinae Oxyphyllae Fructus (AOF) with warming and tonifying the kidney and spleen, anti-salivation, anti-polyuria and anti-diarrhea functions is the dried ripe fruits of Alpinia oxyphylla Miq. (Zingiberaceae). As a traditional Chinese medicine, its application history is very long. AIMS OF THE STUDY: The purpose of our study is to investigate the effects of different solvent extracts from AOF on lipopolysaccharide (LPS)-induced animal model of Alzheimer's disease (AD) to elucidate the traditional medical theories with modern pharmacological methods and provide a reference for further clarifying its active components and mechanisms...
February 12, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29413525/synaptotoxic-signaling-by-amyloid-beta-oligomers-in-alzheimer-s-disease-through-prion-protein-and-mglur5
#19
A Harrison Brody, Stephen M Strittmatter
Alzheimer's disease (AD) represents an impending global health crisis, yet the complexity of AD pathophysiology has so far precluded the development of any interventions to successfully slow or halt AD progression. It is clear that accumulation of Amyloid-beta (Aβ) peptide triggers progressive synapse loss to cause AD symptoms. Once initiated by Aβ, disease progression is complicated and accelerated by inflammation and by tau pathology. The recognition that Aβ peptide assumes multiple distinct states and that soluble oligomeric species (Aβo) are critical for synaptic damage is central to molecular understanding of AD...
2018: Advances in Pharmacology
https://www.readbyqxmd.com/read/29410317/secreted-amyloid-precursor-protein-alpha-activates-neuronal-insulin-receptors-and-prevents-diabetes-induced-encephalopathy
#20
Brent D Aulston, Jason Shapansky, YaWen Huang, Gary L Odero, Gordon W Glazner
Secreted amyloid precursor protein alpha (sAPPα) is a potent neurotrophin in the CNS but a dedicated receptor has not been found. However, protein interactions involving amyloid beta (Aβ), a peptide cleaved from the same parent peptide as sAPPα, indicate that insulin receptors (IRs) could be a target of amyloid peptides. In this study, in vitro analysis of cortical neuronal cultures revealed that exogenous sAPPα increased IR phosphorylation in the absence of insulin. Furthermore, in an APP overexpressing mouse model, sAPPα bound IRs in the cortex with significantly greater binding in hypoinsulinemic animals...
February 2, 2018: Experimental Neurology
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