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https://www.readbyqxmd.com/read/29143217/fluid-biomarker-agreement-and-interrelation-in-dementia-due-to-alzheimer-s-disease
#1
Panagiotis Alexopoulos, Jennifer Roesler, Lukas Werle, Nathalie Thierjung, Iliana Lentzari, Marion Ortner, Timo Grimmer, Nikolaos Laskaris, Antonios Politis, Philippos Gourzis, Alexander Kurz, Robert Perneczky
The cerebrospinal fluid (CSF) levels of β-amyloid 42, total tau, and phosphorylated tau 181 are supposed to be all continuously abnormal in dementia due to Alzheimer's disease (AD), being the most advanced disease stage. The aim of the present study, which included a monocentric and a multicentric sample (N = 119 and 178, respectively), was to investigate the degree of CSF biomarker agreement and interrelation in AD dementia. Based on previously published cut-off values, biomarker values were categorized as positive or negative for AD (dichotomization strategy) and as either positive, negative, or borderline (trichotomization strategy)...
November 15, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29141977/vitamins-associated-with-brain-aging-mild-cognitive-impairment-and-alzheimer-disease-biomarkers-epidemiological-and-experimental-evidence-plausible-mechanisms-and-knowledge-gaps
#2
REVIEW
Michael Fenech
The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141588/parkinson-disease-polygenic-risk-score-is-associated-with-parkinson-disease-status-and-age-at-onset-but-not-with-alpha-synuclein-cerebrospinal-fluid-levels
#3
Laura Ibanez, Umber Dube, Benjamin Saef, John Budde, Kathleen Black, Alexandra Medvedeva, Jorge L Del-Aguila, Albert A Davis, Joel S Perlmutter, Oscar Harari, Bruno A Benitez, Carlos Cruchaga
BACKGROUND: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained. Polygenic risk scores (PRS) may provide greater statistical power and inform about the genetic architecture of multiple phenotypes. The aim of this study was to test the association between PRS and PD risk, age at onset and cerebrospinal fluid (CSF) biomarkers (α-synuclein, Aβ1-42, t-tau and p-tau)...
November 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29141186/hyperbaric-oxygen-therapy-ameliorates-pathophysiology-of-3xtg-ad-mouse-model-by-attenuating-neuroinflammation
#4
Ronit Shapira, Beka Solomon, Shai Efrati, Dan Frenkel, Uri Ashery
There is a real need for new interventions for Alzheimer's disease (AD). Hyperbaric oxygen therapy (HBOT), the medical administration of 100% oxygen at conditions greater than 1 atmosphere absolute, has been used successfully to treat several neurological conditions, but its effects on AD pathology have never been thoroughly examined. Therefore, we exposed old triple-transgenic (3xTg) and non-transgenic mice to HBOT followed by behavioral, histological, and biochemical analyses. HBOT attenuated neuroinflammatory processes by reducing astrogliosis, microgliosis, and the secretion of proinflammatory cytokines (IL-1β and TNFα) and increasing expression of scavenger receptor A, arginase1, and antiinflammatory cytokines (IL-4 and IL-10)...
October 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29138281/a-conserved-cytoskeletal-signaling-cascade-mediates-neurotoxicity-of-ftdp-17-tau-mutations-in-vivo
#5
Farah H Bardai, Liqun Wang, Yamini Mutreja, Mythili Yenjerla, T Chris Gamblin, Mel B Feany
The microtubule binding protein tau is strongly implicated in multiple neurodegenerative disorders, including frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), which is caused by mutations in tau. In vitro, FTDP-17 mutant versions of tau can reduce microtubule binding and increase aggregation of tau, but the mechanism by which these mutations promote disease in vivo is not clear. Here we take a combined biochemical and in vivo modeling approach to define functional properties of tau driving neurotoxicity in vivo We express wild type human tau and five FTDP-17 mutant forms of tau in Drosophila using a site-directed insertion strategy to ensure equivalent levels of expression...
November 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29134321/co-occurrence-of-mixed-proteinopathies-in-late-stage-huntington-s-disease
#6
Isabelle St-Amour, Andréanne Turgeon, Claudia Goupil, Emmanuel Planel, Sébastien S Hébert
Accumulating evidence highlights the potential role of mixed proteinopathies (i.e., abnormal protein aggregation) in the development of clinical manifestations of neurodegenerative diseases (NDD). Huntington's disease (HD) is an inherited NDD caused by autosomal-dominant expanded CAG trinucleotide repeat mutation in the gene coding for Huntingtin (Htt). Previous studies have suggested the coexistence of phosphorylated-Tau, α-synuclein (α-Syn) and TAR DNA-binding protein 43 (TDP-43) inclusions in HD. However, definite evidence that HD pathology in humans can be accompanied by other proteinopathies is still lacking...
November 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29132541/novel-treatment-strategies-using-tio2-nanowired-delivery-of-histaminergic-drugs-and-antibodies-to-tau-with-cerebrolysin-for-superior-neuroprotection-in-the-pathophysiology-of-alzheimer-s-disease
#7
Aruna Sharma, Preeti K Menon, Ranjana Patnaik, Dafin F Muresanu, José V Lafuente, Z Ryan Tian, Asya Ozkizilcik, Rudy J Castellani, Herbert Mössler, Hari S Sharma
More than 5.5 million Americans of all ages are suffering from Alzheimer's disease (AD) till today for which no suitable therapy has been developed so far. Thus, there is an urgent need to explore novel therapeutic measures to contain brain pathology in AD. The hallmark of AD includes amyloid-beta peptide (AβP) deposition and phosphorylation of tau in AD brain. Recent evidences also suggest a marked decrease in neurotrophic factors in AD. Thus, exogenous supplement of neurotrophic factors could be one of the possible ways for AD therapy...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29132216/curcumin-decreases-hyperphosphorylation-of-tau-by-down-regulating-caveolin-1-gsk-3%C3%AE-in-n2a-app695swe-cells-and-app-ps1-double-transgenic-alzheimer-s-disease-mice
#8
Jieyun Sun, Xiong Zhang, Chen Wang, Zhipeng Teng, Yu Li
Caveolin-1, the marker protein of membranal caveolae, is not only involved in cholesterol regulation, but also participates in the cleavage of amyloid [Formula: see text]-protein precursor (APP) and the generation of [Formula: see text]-amyloid peptide. It has been reported to be tightly related with Tau. In our previous studies, curcumin has been confirmed to play a neuroprotective role in Alzheimer's disease (AD), but its effects on Caveolin-1, Tau and their correlation, and the mechanism is still unknown...
November 13, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29128987/comparison-of-olfactory-and-gustatory-disorders-in-alzheimer-s-disease
#9
Minoru Kouzuki, Tetsuya Suzuki, Masaya Nagano, Syouta Nakamura, Yuto Katsumata, Ayumi Takamura, Katsuya Urakami
Patients with Alzheimer's disease (AD) develop olfactory and gustatory disorders. However, the order of failure and relevance of the pathophysiology are unclear. We compared olfactory identification and whole mouth gustation in patients with AD to those with mild cognitive impairment (MCI) and to healthy controls (HC) and assessed correlations with pathophysiology. Patients with AD (n = 40), MCI (n = 34), and HC (n = 40) were recruited. We performed the Odor Stick Identification Test for Japanese (OSIT-J), gustatory test by the intraoral dropping method using taste solutions, Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale Japanese version (ADAS-J cog), Touch Panel-type Dementia Assessment Scale (TDAS), and measurement of amyloid β (Aβ) 42 and phosphorylated tau (p-tau) 181 levels in cerebrospinal fluid (CSF)...
November 11, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29128902/overexpression-of-5-lipoxygenase-worsens-the-phenotype-of-a-mouse-model-of-tauopathy
#10
Phillip F Giannopoulos, Domenico Praticò
Brain accumulation of increasing amount of phosphorylated microtubule associated tau protein is one the major hallmark lesions of Alzheimer's disease (AD) and related tauopathies. Consistent evidence from clinical and animal studies has shown that neuroinflammation characterizes these diseases. The 5-lipoxygenase (5LO) is an enzyme protein whose metabolic products are lipids with potent inflammatory actions. Previously, we showed that blockade of 5LO activation ameliorates the phenotype of the htau transgenic mice...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29127203/receptor-for-advanced-glycation-endproducts-mediates-sepsis-triggered-amyloid-%C3%AE-accumulation-tau-phosphorylation-and-cognitive-impairment
#11
Juciano Gasparotto, Carolina S Girardi, Nauana Somensi, Camila T Ribeiro, José C F Moreira, Monique Michels, Beatriz Sonai, Mariane Rocha, Amanda V Steckert, Tatiana Barichello, João Quevedo, Felipe Dal-Pizzol, Daniel P Gelain
Patients recovering from sepsis have higher rates of CNS morbidities associated with long-lasting impairment of cognitive functions, including neurodegenerative diseases. However, the molecular etiology of these sepsis-induced impairments is unclear. Here, we investigated the role of the receptor for advanced glycation end products (RAGE) in neuroinflammation, neurodegeneration-associated changes, and cognitive dysfunction arising after sepsis recovery. Adult Wistar rats underwent cecal ligation and perforation (CLP), and serum and brain (hippocampus and prefrontal cortex) samples were obtained at days 1, 15, and 30 after the CLP...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29126976/involvement-of-glucose-related-energy-crisis-and-endoplasmic-reticulum-stress-insinuation-of-streptozotocin-induced-alzheimer-s-like-pathology
#12
Joyshree Biswas, Sonam Gupta, Dinesh Kumar Verma, Parul Gupta, Abhishek Singh, Shubhangini Tiwari, Poonam Goswami, Sharad Sharma, Sarika Singh
The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain...
November 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29125490/plasma-proteomic-profiles-of-cerebrospinal-fluid-defined-alzheimer-s-disease-pathology-in-older-adults
#13
Loïc Dayon, Jérôme Wojcik, Antonio Núñez Galindo, John Corthésy, Ornella Cominetti, Aikaterini Oikonomidi, Hugues Henry, Eugenia Migliavacca, Gene L Bowman, Julius Popp
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. OBJECTIVE: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29125485/cognitive-variability-predicts-incident-alzheimer-s-disease-and-mild-cognitive-impairment-comparable-to-a-cerebrospinal-fluid-biomarker
#14
Carey E Gleason, Derek Norton, Eric D Anderson, Michelle Wahoske, Danielle T Washington, Emre Umucu, Rebecca L Koscik, N Maritza Dowling, Sterling C Johnson, Cynthia M Carlsson, Sanjay Asthana
BACKGROUND: Alzheimer's disease (AD) biomarkers are emerging as critically important for disease detection and monitoring. Most biomarkers are obtained through invasive, resource-intense procedures. A cognitive marker, intra-individual cognitive variability (IICV) may provide an alternative or adjunct marker of disease risk for individuals unable or disinclined to undergo lumbar puncture. OBJECTIVE: To contrast risk of incident AD and mild cognitive impairment (MCI) associated with IICV to risk associated with well-established biomarkers: cerebrospinal fluid (CSF) phosphorylated tau protein (p-tau181) and amyloid-β 42 (Aβ42) peptide...
November 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29123923/root-securing-and-brain-fortifying-liquid-upregulates-caveolin-1-in-cell-model-with-alzheimer-s-disease-through-inhibiting-tau-phosphorylation
#15
Depei Yuan, Chuhua Zeng, Qianfeng Chen, Fengjie Wang, Lin Yuan, Yaoqian Zhu, Ziyang Shu, Ning Chen
In order to explore the effect of root-securing and brain-fortifying Liquid- (RSBFL-) mediated caveolin-1 (CAV-1) on phosphorylation of Tau protein and to uncover underlying mechanisms of RSBFL for the prevention and treatment of Alzheimer's disease (AD), hippocampal neurons isolated from neonatal SD rats and cultured in DMEM-F12 medium were induced by exogenous Aβ1-42 to establish a cell model with AD. Meanwhile, pEGFP-C1-CAV1 and CAV1-shRNA plasmids were transfected into hippocampal neurons for CAV-1 overexpression and silence, respectively...
2017: Neurology Research International
https://www.readbyqxmd.com/read/29121589/pharmacological-targeting-of-gsk-3-and-nrf2-provides-neuroprotection-in-a-preclinical-model-of-tauopathy
#16
Antonio Cuadrado, Sebastian Kügler, Isabel Lastres-Becker
Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF), an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs) from wild type or KEAP1-deficient mice...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29121398/protein-phosphatase-2a-and-tau-an-orchestrated-pas-de-deux
#17
REVIEW
Goce Taleski, Estelle Sontag
The neuronal microtubule-associated protein tau serves a critical role in regulating axonal microtubule dynamics to support neuronal and synaptic functions. Furthermore, it contributes to glutamatergic regulation and synaptic plasticity. Emerging evidence also suggests that tau serves as a signaling scaffold. Tau function and subcellular localisation are tightly regulated, in part, by the orchestrated interplay between phosphorylation and dephosphorylation events. Significantly, protein phosphatase type 2A (PP2A), encompassing the regulatory PPP2R2A (or Bα) subunit, is a major brain heterotrimeric enzyme and the primary tau Ser/Thr phosphatase in vivo...
November 9, 2017: FEBS Letters
https://www.readbyqxmd.com/read/29118695/synapse-innervation-and-associative-memory-cell-are-recruited-for-integrative-storage-of-whisker-and-odor-signals-in-the-barrel-cortex-through-mirna-mediated-processes
#18
Zhuofan Lei, Dangui Wang, Na Chen, Ke Ma, Wei Lu, Zhenhua Song, Shan Cui, Jin-Hui Wang
Associative learning is a common way for information acquisition, and the integrative storage of multiple associated signals is essential for associative thinking and logical reasoning. In terms of the cellular mechanism for associative memory, our studies by behavioral task and cellular imaging demonstrate that paired whisker and odor stimulations lead to odorant-induced whisker motion and associative memory cell recruitment in the barrel cortex (BC), which is driven presumably by synapse innervation from co-activated sensory cortices...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29114726/concordance-between-different-amyloid-immunoassays-and-visual-amyloid-positron-emission-tomographic-assessment
#19
Shorena Janelidze, Josef Pannee, Alvydas Mikulskis, Ping Chiao, Henrik Zetterberg, Kaj Blennow, Oskar Hansson
Importance: Visual assessment of amyloid positron emission tomographic (PET) images has been approved by regulatory authorities for clinical use. Several immunoassays have been developed to measure β-amyloid (Aβ) 42 in cerebrospinal fluid (CSF). The agreement between CSF Aβ42 measures from different immunoassays and visual PET readings may influence the use of CSF biomarkers and/or amyloid PET assessment in clinical practice and trials. Objective: To determine the concordance between CSF Aβ42 levels measured using 5 different immunoassays and visual amyloid PET analysis...
November 6, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29111028/csf-biomarkers-%C3%AE-amyloid-tau-proteins-and-a-synuclein-in-the-differential-diagnosis-of-parkinson-plus-syndromes
#20
Vasilios C Constantinides, George P Paraskevas, Evangelia Emmanouilidou, Olga Petropoulou, Anastasia Bougea, Kostas Vekrellis, Ioannis Evdokimidis, Eleftherios Stamboulis, Elisabeth Kapaki
INTRODUCTION: Differential diagnosis of Parkinson-plus patients (PSP, CBD, MSA) and Parkinson's disease (PD) patients is often not straightforward, particularly in atypical cases or at the initial stages of the diseases. Classic CSF biomarkers (amyloid-beta - Aβ42, tau protein - τT and phosphorylated tau protein - τP-181) are established biomarkers in the diagnosis of Alzheimer's disease (AD). CSF a-synuclein (α-syn) has emerged as a promising biomarker in patients with Parkinsonism...
November 15, 2017: Journal of the Neurological Sciences
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