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https://www.readbyqxmd.com/read/28644588/clinical-consensus-guidelines-on-the-application-of-cerebrospinal-fluid-biomarkers-for-alzheimer-s-disease-diagnosis-recommendations-of-the-irish-network-for-biomarkers-in-neurodegeneration
#1
A M Miller, E Begley, R Coen, M Doyle, J Dunne, S Hutchinson, S P Kennelly, R A Kenny, R P Killeen, A Lynch, S O'Dwyer, C O'Neill, S S O'Sullvan, M J Rowan, N Sheehy, C McGuigan, B A Lawlor
It is accepted that a lumbar puncture (LP) and cerebrospinal fluid (CSF) biomarker analysis support the routine diagnostic work-up for the differential diagnosis of dementia due to Alzheimer's disease (AD) within certain patient cohorts1. These tests, which measure CSF protein concentrations of amyloid-β42 (Aβ42), total tau (t-tau) and phospho tau (p-tau), were recently validated, accredited and made available clinically for the first time in Ireland. A working group, comprising Irish clinical and scientific researchers, met to review a) the validation results; b) international consensus opinions, and c) research and clinical evidence as to the clinical utility of CSF biomarker analysis for AD dementia diagnosis...
December 12, 2016: Irish Medical Journal
https://www.readbyqxmd.com/read/28641164/protective-effects-of-flavonoids-against-alzheimer-s-disease-related-neural-dysfunctions
#2
REVIEW
Mahsa Bakhtiari, Yunes Panahi, Javad Ameli, Behrad Darvishi
Senile ages of human life is mostly associated with developmental of several neurological complicated conditions including decreased cognition and reasoning, increased memory loss and impaired language performance. Alzheimer's disease (AD) is the most prevalent neural disorder associated with dementia, consisting of about 70% of dementia reported cases. Failure of currently approved chemical anti-AD therapeutic agents has once again brought up the idea of administering naturally occurring compounds as effective alternative and/or complementary regimens in AD treatment...
June 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28641077/inhibition-of-early-growth-response-1-in-the-hippocampus-alleviates-neuropathology-and-improves-cognition-in-an-alzheimer-model-with-plaques-and-tangles
#3
Xike Qin, Yunling Wang, Hemant K Paudel
A sporadic form of Alzheimer disease (AD) and vascular dementia share many risk factors, and their pathogenic mechanisms are suggested to be related. Transcription factor early growth response 1 (Egr-1) regulates various vascular pathologies and is up-regulated in both AD brains and AD mouse models; however, its role in AD pathogenesis is unclear. Herein, we report that silencing of Egr-1 in the hippocampus by shRNA reduces tau phosphorylation, amyloid-β (Aβ) pathology, and improves cognition in the 3xTg-AD mouse model...
June 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28640595/detection-and-characterization-of-small-molecule-interactions-with-fibrillar-protein-aggregates-using-microscale-thermophoresis
#4
Emily Fisher, Yanyan Zhao, Robert Richardson, Malgorzata Janik, Alexander K Buell, Franklin I Aigbirhio, Gergely Toth
Neurodegenerative diseases such as Parkinson's and Alzheimer's disease share the pathological hallmark of fibrillar protein aggregates. The specific detection of these protein aggregates by positron emission tomography (PET) in the patient brain can yield valuable information for diagnosis and disease progression. However, the identification of novel small compounds that bind fibrillar protein aggregates has been a challenge. In this study, microscale thermophoresis (MST) was applied to assess the binding affinity of known small molecule ligands of α-synuclein fibrils, which were also tested in parallel in a Thioflavin T fluorescence competition assay for further validation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28638989/parietal-white-matter-lesions-in-alzheimer-s-disease-are-associated-with-cortical-neurodegenerative-pathology-but-not-with-small-vessel-disease
#5
Kirsty E McAleese, Lauren Walker, Sophie Graham, Elisa L J Moya, Mary Johnson, Daniel Erskine, Sean J Colloby, Madhurima Dey, Carmen Martin-Ruiz, John-Paul Taylor, Alan J Thomas, Ian G McKeith, Charles De Carli, Johannes Attems
Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. hyperphosphorylated tau (HPτ) and amyloid-beta (Aβ) deposition. WML seen in AD have a posterior predominance compared to non-demented individuals but it is unclear whether the pathological and molecular signatures of WML differ between these two groups...
June 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28638201/a-pilot-longitudinal-study-on-cerebrospinal-fluid-csf-tau-protein-in-alzheimer-s-disease-and-vascular-dementia
#6
Haihong Wang, Tao Wang, Shixing Qian, Li Ba, Zhiguang Lin, Shifu Xiao
BACKGROUND: Alzheimer's disease (AD) has high a prevalence rate, high medical costs, and care difficulties, and has become a serious social and economic problem in our aging society. So far, there has not been a reliable and objective diagnostic criteria for AD found. In recent years, there have been many domestic and foreign studies on the biological markers of cerebrospinal fluid in the patients with AD, and high levels of the T-tau, P-tau found in cerebrospinal fluid (CSF) is at this point an indisputable fact...
October 25, 2016: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28637381/role-of-caspase-3-mediated-apoptosis-in-chronic-caspase-3-cleaved-tau-accumulation-and-blood-brain-barrier-damage-in-the-corpus-callosum-after-traumatic-brain-injury-in-rats
#7
Olena Glushakova, Andriy O Glushakov, Cesar Borlongan, Alex Valadka, Ronald L Hayes, Alexander V Glushakov
Traumatic brain injury (TBI) may be a significant risk factor for development of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE), post-traumatic epilepsy (PTE), and Alzheimer's (AD) and Parkinson's (PD) diseases. Chronic TBI is associated with several pathological features that are also characteristic of neurodegenerative diseases, including tau pathologies, caspase-3-mediated apoptosis, neuroinflammation, and microvascular alterations. The goal of this study was to evaluate changes following TBI in cleaved-caspase-3 and caspase-3-cleaved tau truncated at Asp421 and their relationships to cellular markers potentially associated with inflammation and blood-brain (BBB) barrier damage...
June 22, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28636913/heterogeneous-tau-tubulin-complexes-accelerate-microtubule-polymerization
#8
Xiao-Han Li, Elizabeth Rhoades
Tau is an intrinsically disordered protein with a central role in the pathology of a number of neurodegenerative diseases. Tau normally functions to stabilize neuronal microtubules, although the mechanism underlying this function is not well understood. Of note is that the interaction between tau and soluble tubulin, which has implications both in understanding tau function as well as its role in disease, is underexplored. Here we investigate the relationship between heterogeneity in tau-tubulin complexes and tau function...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28634862/effect-of-gapt-extract-on-expression-of-tau-protein-and-its-phosphorylation-related-enzymes-in-hippocampal-neurons-of-appv717i-transgenic-mice
#9
Jing-Nian Ni, Jing Shi, Xue-Kai Zhang, Yi-Chang Yang, Xiao-Meng Liu, Ming-Qing Wei, Ting Li, Peng-Wen Wang, Jin-Zhou Tian, Yong-Yan Wang
OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg d)], the low, medium and high dosage of GAPT groups [0...
June 20, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28634382/expression-of-p301l-htau-in-mouse-mec-induces-hippocampus-dependent-memory-deficit
#10
Xinghua Liu, Kuan Zeng, Mengzhu Li, Qun Wang, Rong Liu, Bin Zhang, Jian-Zhi Wang, Xiji Shu, Xiaochuan Wang
Intracellular accumulation of abnormally phosphorylated tau in different types of neurons is a pathological characteristic of Alzheimer's disease (AD). While tau modification and associated neuronal loss and hypometabolism start in the entorhinal cortex (EC) in early AD patients, the mechanism by which mutant P301L hTau leads to dementia is not fully elucidated. Here, we studied the effects of P301L hTau transduction in the medial EC (MEC) of mice on tau phosphorylation and accumulation, and cognitive deficit...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634349/synuclein-impairs-trafficking-and-signaling-of-bdnf-in-a-mouse-model-of-parkinson-s-disease
#11
Fang Fang, Wanlin Yang, Jazmin B Florio, Edward Rockenstein, Brian Spencer, Xavier M Orain, Stephanie X Dong, Huayan Li, Xuqiao Chen, Kijung Sung, Robert A Rissman, Eliezer Masliah, Jianqing Ding, Chengbiao Wu
Recent studies have demonstrated that hyperphosphorylation of tau protein plays a role in neuronal toxicities of α-synuclein (ASYN) in neurodegenerative disease such as familial Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease. Using a transgenic mouse model of Parkinson's disease (PD) that expresses GFP-ASYN driven by the PDGF-β promoter, we investigated how accumulation of ASYN impacted axonal function. We found that retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF) in DIV7 cultures of E18 cortical neurons was markedly impaired at the embryonic stage, even though hyperphosphorylation of tau was not detectable in these neurons at this stage...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632947/pimozide-reduces-toxic-forms-of-tau-in-tauc3-mice-via-ampk-mediated-autophagy
#12
YoungDoo Kim, Eun Il Jeong, Jihoon Nah, Seung-Min Yoo, WonJae Lee, Youbin Kim, Seowon Moon, Se-Hoon Hong, Yong-Keun Jung
In neurodegenerative diseases like Alzheimer's disease (AD), tau is hyperphosphorylated and forms aggregates and neurofibrillary tangles in affected neurons. Autophagy is critical to clear the aggregates of disease-associated proteins and is often altered in patients and animal models of AD. Because mTOR (mechanistic target of rapamycin) negatively regulates autophagy and is hyperactive in the brains of patients with AD, mTOR is an attractive therapeutic target for AD. However, pharmacological strategies to increase autophagy by targeting mTOR inhibition cause various side effects...
June 20, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28632177/the-intersection-of-ngf-trka-signaling-and-amyloid-precursor-protein-processing-in-alzheimer-s-disease-neuropathology
#13
REVIEW
Nadia Canu, Giuseppina Amadoro, Viviana Triaca, Valentina Latina, Valentina Sposato, Veronica Corsetti, Cinzia Severini, Maria Teresa Ciotti, Pietro Calissano
Dysfunction of nerve growth factor (NGF) and its high-affinity Tropomyosin receptor kinase A (TrkA) receptor has been suggested to contribute to the selective degeneration of basal forebrain cholinergic neurons (BFCN) associated with the progressive cognitive decline in Alzheimer's disease (AD). The aim of this review is to describe our progress in elucidating the molecular mechanisms underlying the dynamic interplay between NGF/TrkA signaling and amyloid precursor protein (APP) metabolism within the context of AD neuropathology...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28629249/increase-of-neuronal-injury-markers-tau-and-neurofilament-light-proteins-in-umbilical-blood-after-intrapartum-asphyxia
#14
Hanna Toorell, Henrik Zetterberg, Blennow, Karin Sävman, Henrik Hagberg
Fetal asphyxia remains a clinical problem resulting in life-long neurologic disabilities. We urgently need more accurate early predictive markers to direct the clinician when to provide neuroprotective therapy. In the present study, we analyzed the neuronal proteins Tau and neurofilament light proteins in umbilical blood of 10 cases of severe-moderate intrapartum asphyxia and in 18 control cases. The levels of both Tau and neurofilament were significantly higher after asphyxia and it appeared to be a correlation between the levels of the biomarkers and the severity of the insult...
June 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28628634/protein-signature-in-cerebrospinal-fluid-and-serum-of-alzheimer-s-disease-patients-the-case-of-apolipoprotein-a-1-proteoforms
#15
Chiara Fania, Beatrice Arosio, Daniele Capitanio, Enrica Torretta, Cristina Gussago, Evelyn Ferri, Daniela Mari, Cecilia Gelfi
In the diagnosis of Alzheimer's disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several "confounding" factors including intra- and inter-individual, pre-analytical and analytical variabilities...
2017: PloS One
https://www.readbyqxmd.com/read/28626751/feeder-cell-type-affects-the-growth-of-in-vitro-cultured-bovine-trophoblast-cells
#16
Islam M Saadeldin, Ahmed Abdelfattah-Hassan, Ayman Abdel-Aziz Swelum
Trophectoderm cells are the foremost embryonic cells to differentiate with prospective stem-cell properties. In the current study, we aimed at improving the current approach for trophoblast culture by using granulosa cells as feeders. Porcine granulosa cells (PGCs) compared to the conventional mouse embryonic fibroblasts (MEFs) were used to grow trophectoderm cells from hatched bovine blastocysts. Isolated trophectoderm cells were monitored and displayed characteristic epithelial/cuboidal morphology. The isolated trophectoderm cells expressed mRNA of homeobox protein (CDX2), cytokeratin-8 (KRT8), and interferon tau (IFNT)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28624654/insulin-signaling-an-opportunistic-target-to-minify-risk-of-alzheimer-s-disease
#17
REVIEW
Rohit Pardeshi, Nityanand Bolshette, Kundlik Gadhave, Ashutosh Ahire, Sahabuddin Ahmed, Tommaso Cassano, Veer Bala Gupta, Mangala Lahkar
Alzheimer's disease (AD) is progressive neurodegenerative disorder characterized by accumulation of senile plaques, neurofibrillary tangles (NFT) and neurodegeneration. The diabetes mellitus (DM) is one of the risk factors for AD pathogenesis by impairment in insulin signaling and glucose metabolism in central as well as peripheral system. Insulin resistance, impaired glucose and lipid metabolism lead to the Aβ (Aβ) aggregation, Tau phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, memory impairment and also mark over Aβ transport through central to peripheral and vice versa...
May 30, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28623460/spreading-of-pathology-in-alzheimer-s-disease
#18
REVIEW
Zhong-Yue Lv, Chen-Chen Tan, Jin-Tai Yu, Lan Tan
The senile plaques (SPs) and neurofibrillary tangles (NFTs) are the two major pathological hallmarks of AD, which are composed of β-amyloid protein and Tau protein. So the β-amyloid protein (Aβ) and Tau oligomers (oTau) are the majority in the pathology of AD. Recently, the spreading of Aβ and oTau in the brain of AD patients has received heated value. In this review, we summarize recent research progress and aim to figure out the spreading mechanism of Aβ and Tau in AD via introduction of the formation, release, uptake, diffusion between different brain regions, and the propagation principle of Aβ and Tau...
June 16, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28623194/quantitative-mapping-of-microtubule-associated-protein-2c-map2c-phosphorylation-and-regulatory-protein-14-3-3%C3%AE-binding-sites-reveals-key-differences-between-map2c-and-its-homolog-tau
#19
Séverine Jansen, Kateřina Melková, Zuzana Trošanová, Kateřina Hanáková, Milan Zachrdla, Jiři Nováček, Erik Župa, Zbyněk Zdráhal, Jozef Hritz, Lukáš Žídek
No abstract text is available yet for this article.
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#20
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
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