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Amyloid beta tau protein

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https://www.readbyqxmd.com/read/27895577/fus1-ko-mouse-as-a-model-of-oxidative-stress-mediated-sporadic-alzheimer-s-disease-circadian-disruption-and-long-term-spatial-and-olfactory-memory-impairments
#1
Guillermo Coronas-Samano, Keeley L Baker, Winston J T Tan, Alla V Ivanova, Justus V Verhagen
Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD) these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27884163/chronic-adiponectin-deficiency-leads-to-alzheimer-s-disease-like-cognitive-impairments-and-pathologies-through-ampk-inactivation-and-cerebral-insulin-resistance-in-aged-mice
#2
Roy Chun-Laam Ng, On-Yin Cheng, Min Jian, Jason Shing-Cheong Kwan, Philip Wing-Lok Ho, Kenneth King-Yip Cheng, Patrick Ka Kit Yeung, Lena Lei Zhou, Ruby Lai-Chong Hoo, Sookja Kim Chung, Aimin Xu, Karen Siu-Ling Lam, Koon Ho Chan
BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM...
November 25, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27844089/-biomarkers-for-dementia-and-other-neurodegenerative-diseases-current-developments
#3
J Wiltfang, P Lewczuk, M Otto
Cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD) support the early and differential diagnosis of dementia, most importantly the diagnosis of early or preclinical Alzheimer's dementia (AD). Meanwhile CSF-NDD are now recommended for improved exclusion and positive diagnostics of AD by the German national neuropsychiatry S3 dementia guidelines ( www.DGPPN.de ). Meta-analyses of independent international multicenter studies have shown that a combined CSF analysis of amyloid-beta 1-42 (Aβ 1-42, decreased), total tau proteins (increased) and phospho-tau proteins (increased) offers a sensitivity and specificity of 80-90 % for the early and differential diagnosis of AD (AD versus all other)...
November 14, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27842611/tau-pathology-in-aged-cynomolgus-monkeys-is-progressive-supranuclear-palsy-corticobasal-degeneration-but-not-alzheimer-disease-like-ultrastructural-mapping-of-tau-by-edx
#4
Toshiki Uchihara, Kentaro Endo, Hiromi Kondo, Sachi Okabayashi, Nobuhiro Shimozawa, Yasuhiro Yasutomi, Eijiro Adachi, Nobuyuki Kimura
Concomitant deposition of amyloid -beta protein (Aβ) and neuronal tau as neurofibrillary tangles in the human brain is a hallmark of Alzheimer disease (AD). Because these deposits increase during normal aging, it has been proposed that aging brains may also undergo AD-like changes. To investigate the neuropathological changes that occur in the aging primate brain, we examined 21 brains of cynomolgus monkeys (7-36 years old) for Aβ- and tau-positive lesions. We found, 1) extensive deposition of Aβ in brains of cynomolgus monkeys over 25 years of age, 2) selective deposition of 4-repeat tau as pretangles in neurons, and as coiled body-like structures in oligodendroglia-like cells and astrocytes, 3) preferential distribution of tau in the basal ganglia and neocortex rather than the hippocampus, and 4) age-associated increases in 30-34 kDa AT8- and RD4-positive tau fragments in sarkosyl-insoluble fractions...
November 14, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27832767/chitinase-3-like-1-protein-chi3l1-locus-influences-cerebrospinal-fluid-levels-of-ykl-40
#5
Yuetiva Deming, Kathleen Black, David Carrell, Yefei Cai, Jorge L Del-Aguila, Maria Victoria Fernandez, John Budde, ShengMei Ma, Benjamin Saef, Bill Howells, Sarah Bertelsen, Kuan-Lin Huang, Courtney L Sutphen, Rawan Tarawneh, Anne M Fagan, David M Holtzman, John C Morris, Alison M Goate, Joseph D Dougherty, Carlos Cruchaga
BACKGROUND: Alzheimer's disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ42 ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (Aβ42) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers...
November 10, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27815990/low-level-laser-therapy-for-beta-amyloid-toxicity-in-rat-hippocampus
#6
Yujiao Lu, Ruimin Wang, Yan Dong, Donovan Tucker, Ningjun Zhao, Md Ejaz Ahmed, Ling Zhu, Timon Cheng-Yi Liu, Robert M Cohen, Quanguang Zhang
Beta amyloid (Aβ) is well accepted to play a central role in the pathogenesis of Alzheimer's disease (AD). The present work evaluated the therapeutic effects of low-level laser irradiation (LLI) on Aβ-induced neurotoxicity in rat hippocampus. Aβ 1-42 was injected bilaterally to the hippocampus CA1 region of adult male rats, and 2-minute daily LLI treatment was applied transcranially after Aβ injection for 5 consecutive days. LLI treatment suppressed Aβ-induced hippocampal neurodegeneration and long-term spatial and recognition memory impairments...
October 11, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27809235/protective-effect-of-genistein-against-neuronal-degeneration-in-apoe-mice-fed-a-high-fat-diet
#7
Yoon-Jin Park, Je Won Ko, Sookyoung Jeon, Young Hye Kwon
Altered cholesterol metabolism is believed to play a causal role in major pathophysiological changes in neurodegeneration. Several studies have demonstrated that the absence of apolipoprotein E (ApoE), a predominant apolipoprotein in the brain, leads to an increased susceptibility to neurodegeneration. Previously, we observed that genistein, a soy isoflavone, significantly alleviated apoptosis and tau hyperphosphorylation in SH-SY5Y cells. Therefore, we investigated the neuroprotective effects of dietary genistein supplementation (0...
October 31, 2016: Nutrients
https://www.readbyqxmd.com/read/27794478/amyloid-beta-modulators-and-neuroprotection-in-alzheimer-s-disease-a-critical-appraisal
#8
REVIEW
Chandra Sekhar Kuruva, P Hemachandra Reddy
Multiple cellular changes have been identified as being involved in Alzheimer's disease (AD) pathogenesis, including mitochondrial damage, synaptic loss, amyloid beta (Aβ) production and/or accumulation, inflammatory responses, and phosphorylated tau formation and/or accumulation. Studies have established that Aβ-induced synaptic dysfunction is dependent on abnormal amyloid precursor protein (APP) processing caused by β- and γ-secretases, resulting in the generation of Aβ. The Aβ formed as a result of abnormal APP processing induces phosphorylated tau and activates glycogen synthase kinase-3β (GSK3β) and cyclin-dependent kinase-5 (CDK5)...
October 26, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27764160/csf-biomarkers-and-its-associations-with-18f-av133-cerebral-vmat2-binding-in-parkinson-s-disease-a-preliminary-report
#9
Rui Gao, Guangjian Zhang, Xueqi Chen, Aimin Yang, Gwenn Smith, Dean F Wong, Yun Zhou
OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers, such as α-synuclein (α-syn), amyloid beta peptide 1-42 (Aβ1-42), phosphorylated tau (181P) (p-tau), and total tau (t-tau), have long been associated with the development of Parkinson disease (PD) and other neurodegenerative diseases. In this investigation, we reported the assessment of CSF biomarkers and their correlations with vesicular monoamine transporter 2 (VMAT2) bindings measured with 18F-9-fluoropropyl-(+)-dihydrotetrabenazine (18F-AV133) that is being developed as a biomarker for PD...
2016: PloS One
https://www.readbyqxmd.com/read/27761145/neuroprotective-effects-of-the-herbal-formula-b401-in-both-cell-and-mouse-models-of-alzheimer-s-disease
#10
Chih-Hsiang Hsu, Sheue-Er Wang, Ching-Lung Lin, Chun-Jen Hsiao, Shuenn-Jyi Sheu, Chung-Hsin Wu
In this study, we have reported the herbal formula B401 that has neuroprotective effects via multifunction, multitarget characteristics. It is possible that the herbal formula B401 may also provide new insights for AD. Here, we studied protective effects in the Tet-On Aβ42-GFP SH-SY5Y cell model and the APP/PS1/Tau triple transgenic mouse model by the herbal formula B401. In in vitro experiments, we showed that the herbal formula B401 treatment effectively reduces glutamate-induced excitotoxicity and acetylcholinesterase activity in Tet-On Aβ42-GFP SH-SY5Y cells...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27760398/immunopegliposome-mediated-reduction-of-blood-and-brain-amyloid-levels-in-a-mouse-model-of-alzheimer-s-disease-is-restricted-to-aged-animals
#11
Lara Ordóñez-Gutiérrez, Adrián Posado-Fernández, Davoud Ahmadvand, Barbara Lettiero, Linping Wu, Marta Antón, Orfeu Flores, Seyed Moein Moghimi, Francisco Wandosell
The accumulation of extracellular amyloid-beta (Aβ) and intracellular neurofibrillary tangles (hyper-phosphorylated Tau) in the brain are two major neuropathological hallmarks of Alzheimer's disease (AD). Active and passive immunotherapy may limit cerebral Aβ deposition and/or accelerate its clearance. With the aid of a newly characterized monoclonal anti-Aβ antibody we constructed immunoPEGliposomes with high avidity for capturing Aβ in the periphery. The functionality of these vesicles in modulating Aβ uptake by both human brain capillary endothelial hCMEC/D3 cells (suppressing uptake) and THP-1 phagocytes (stimulating uptake) was confirmed in vitro...
August 2, 2016: Biomaterials
https://www.readbyqxmd.com/read/27756054/bioactive-effects-of-quercetin-in-the-central-nervous-system-focusing-on-the-mechanisms-of-actions
#12
Natarajan Suganthy, Kasi Pandima Devi, Seyed Fazel Nabavi, Nady Braidy, Seyed Mohammad Nabavi
Quercetin, a ubiquitous flavonoid that is widely distributed in plants is classified as a cognitive enhancer in traditional and oriental medicine. The protective effects of quercetin for the treatment of neurodegenerative disorders and cerebrovascular diseases have been demonstrated in both in vitro and in vivo studies. The free radical scavenging activity of quercetin has been well-documented, wherein quercetin has been observed to exhibit protective effects against oxidative stress mediated neuronal damage by modulating the expression of NRF-2 dependent antioxidant responsive elements, and attenuation of neuroinflammation by suppressing NF-κB signal transducer and activator of transcription-1 (STAT-1)...
October 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27750032/prevention-of-tau-increase-in-cerebrospinal-fluid-of-app-transgenic-mice-suggests-downstream-effect-of-bace1-inhibition
#13
Juliane Schelle, Lisa Häsler, Jens C Göpfert, Thomas O Joos, Hugo Vanderstichele, Erik Stoops, Ulf Neumann, Derya R Shimshek, Matthias Staufenbiel, Mathias Jucker, Stephan A Kaeser
INTRODUCTION: The inhibition of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is a main therapeutic approach for the treatment of Alzheimer's disease (AD). We previously reported an age-related increase of tau protein in the cerebrospinal fluid (CSF) of Aβ precursor protein (APP) transgenic mice. METHODS: APP transgenic mice were treated with a potent BACE1 inhibitor. CSF tau and CSF Aβ levels were assessed. A novel high-sensitivity tau sandwich immunoassay was developed...
October 14, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27730512/anthocyanin-loaded-peg-gold-nanoparticles-enhanced-the-neuroprotection-of-anthocyanins-in-an-a%C3%AE-1-42-mouse-model-of-alzheimer-s-disease
#14
Tahir Ali, Min Ju Kim, Shafiq Ur Rehman, Ashfaq Ahmad, Myeong Ok Kim
Nanomedicine is an emerging research area. In this study, we investigated the neuroprotective efficacy of anthocyanin-loaded polyethylene glycol-gold nanoparticles (PEG-AuNPs) for enhancing the neuroprotective efficacy of anthocyanins in an amyloid beta (Aβ)1-42 mouse model of Alzheimer's disease. We observed that both anthocyanin-loaded PEG-AuNPs and anthocyanins treatment (12 μg/g/day for 14 days) ameliorated memory impairments in the Aβ1-42-injected mice. However, the anthocyanin-loaded PEG-AuNPs were more effective than free anthocyanins...
October 11, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27718298/changes-in-the-detergent-insoluble-brain-proteome-linked-to-amyloid-and-tau-in-alzheimer-s-disease-progression
#15
Chadwick M Hales, Eric B Dammer, Qiudong Deng, Duc M Duong, Marla Gearing, Juan C Troncoso, Madhav Thambisetty, James J Lah, Joshua M Shulman, Allan I Levey, Nicholas T Seyfried
Despite a key role of amyloid-beta (Aβ) in Alzheimer's disease (AD), mechanisms that link Aβ plaques to tau neurofibrillary tangles and cognitive decline still remain poorly understood. The purpose of this study was to quantify proteins in the sarkosyl-insoluble brain proteome correlated with Aβ and tau insolubility in the asymptomatic phase of AD (AsymAD) and through mild cognitive impairment (MCI) and symptomatic AD. Employing label-free mass spectrometry based proteomics, we quantified 2,711 sarkosyl-insoluble proteins across the prefrontal cortex from 35 individual cases representing control, AsymAD, MCI and AD...
October 8, 2016: Proteomics
https://www.readbyqxmd.com/read/27712576/multiple-targets-for-management-of-alzheimer-s-disease-a-review
#16
Sayeed Ahmad, Salman Akhtar, Qazi Mohammad Sajid Jamal, Syed Mohd Danish Rizvi, Mohammad A Kamal, M Kalim A Khan, Mohd Haris Siddiqui
AD is a progressive and irreversible neurodegenerative disease and the most common cause of dementia in the elderly population. Βeta- amyloid cascade formation along with several cytoskeleton abnormalities succeeding to the hyperphosphorylation of microtubule-associated tau protein in neurons leads to the elicitation of several neurotoxic incidents. As an outcome of these phenomena, steady growth of dementia in aged population is becoming ubiquitous in both developed and developing countries. Thus, the key aspiration is to endow with stable daily life functionality to the person suffering from dementia and to cut down or slower the symptoms of disease leading to disruptive behavior...
October 3, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27706423/aged-lewis-rats-exposed-to-low-and-moderate-doses-of-rotenone-are-a-good-model-for-studying-the-process-of-protein-aggregation-and-its-effects-upon-central-nervous-system-cell-physiology
#17
Michael F Almeida, Carolliny M Silva, Aline M D'Unhao, Merari F R Ferrari
Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot...
September 2016: Arquivos de Neuro-psiquiatria
https://www.readbyqxmd.com/read/27701410/brain-derived-neurotrophic-factor-protects-against-tau-related-neurodegeneration-of-alzheimer-s-disease
#18
S-S Jiao, L-L Shen, C Zhu, X-L Bu, Y-H Liu, C-H Liu, X-Q Yao, L-L Zhang, H-D Zhou, D G Walker, J Tan, J Götz, X-F Zhou, Y-J Wang
Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aβ-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established...
October 4, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27699422/methylene-blue-the-long-and-winding-road-from-stain-to-brain-part-2
#19
Robert H Howland
Methylene blue was the first synthetic drug ever used in medicine, having been used to treat clinical pain syndromes, malaria, and psychotic disorders more than one century ago. Methylene blue is a cationic thiazine dye with redox-cycling properties and a selective affinity for the nervous system. This drug also inhibits the activity of monoamine oxidase, nitric oxide synthase, and guanylyl cyclase, as well as tau protein aggregation; increases the release of neurotransmitters, such as serotonin and norepinephrine; reduces amyloid-beta levels; and increases cholinergic transmission...
October 1, 2016: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/27697064/targeting-tumor-necrosis-factor-alpha-for-alzheimer-s-disease
#20
Boris Decourt, Debomoy K Lahiri, Marwan N Sabbagh
Alzheimer's disease (AD) affects an estimated 44 million individuals worldwide, yet no therapeutic intervention is available to stop the progression of the dementia. Neuropathological hallmarks of AD are extracellular deposits of amyloid beta (Aβ) peptides into plaques, intraneuronal accumulation of hyperphosphorylated tau protein forming tangles, and chronic inflammation. A pivotal molecule in inflammation is the pro-inflammatory cytokine TNF-α. Several lines of evidence using genetic and pharmacological manipulations indicate that TNF-α signaling exacerbates both Aβ and tau pathologies in vivo...
September 30, 2016: Current Alzheimer Research
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