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https://www.readbyqxmd.com/read/29156571/studies-for-improving-a-rat-model-of-alzheimer-s-disease-icv-administration-of-well-characterized-%C3%AE-amyloid-1-42-oligomers-induce-dysfunction-in-spatial-memory
#1
Ágnes Kasza, Botond Penke, Zsuzsanna Frank, Zsolt Bozsó, Viktor Szegedi, Ákos Hunya, Klaudia Németh, Gábor Kozma, Lívia Fülöp
During the past 15 years, several genetically altered mouse models of human Alzheimer's disease (AD) have been developed. These costly models have greatly facilitated the evaluation of novel therapeutic approaches. Injecting synthetic β-amyloid (Aβ) 1-42 species into different parts of the brain of non-transgenic rodents frequently provided unreliable results, owing to a lack of a genuine characterization of the administered Aβ aggregates. Previously, we have published a new rat AD-model in which protofibrillar-fibrillar Aβ1-42 was administered into rat entorhinal cortex (Sipos 2007)...
November 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29155947/dementia-after-moderate-severe-traumatic-brain-injury-coexistence-of-multiple-proteinopathies
#2
Kimbra Kenney, Diego Iacono, Brian L Edlow, Douglas I Katz, Ramon Diaz-Arrastia, Kristen Dams-O'Connor, Daniel H Daneshvar, Allison Stevens, Allison L Moreau, Lee S Tirrell, Ani Varjabedian, Anastasia Yendiki, Andre van der Kouwe, Azma Mareyam, Jennifer A McNab, Wayne A Gordon, Bruce Fischl, Ann C McKee, Daniel P Perl
We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI...
November 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29155708/enrichment-of-detergent-insoluble-protein-aggregates-from-human-postmortem-brain
#3
Ian Diner, Tram Nguyen, Nicholas T Seyfried
In this study, we describe an abbreviated single-step fractionation protocol for the enrichment of detergent-insoluble protein aggregates from human postmortem brain. The ionic detergent N-lauryl-sarcosine (sarkosyl) effectively solubilizes natively folded proteins in brain tissue allowing the enrichment of detergent-insoluble protein aggregates from a wide range of neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis, and prion diseases...
October 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29154608/a-life-stress-emotional-awareness-and-expression-interview-for-primary-care-patients-with-medically-unexplained-symptoms-a-randomized-controlled-trial
#4
Maisa S Ziadni, Jennifer N Carty, Heather K Doherty, John H Porcerelli, Lisa J Rapport, Howard Schubiner, Mark A Lumley
OBJECTIVE: Lifetime trauma, relationship adversities, and emotional conflicts are elevated in primary care patients with medically unexplained symptoms (MUS), and these risk factors likely trigger or exacerbate symptoms. Helping patients disclose stressors, increase awareness and expression of inhibited emotions, and link emotions to physical symptoms may improve health. We developed an emotional awareness and expression interview that targets stressful life experiences and conflicts and then tested its effects on primary care patients with MUS...
November 20, 2017: Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association
https://www.readbyqxmd.com/read/29154286/clinic-based-validation-of-cerebrospinal-fluid-biomarkers-with-florbetapir-pet-for-diagnosis-of-dementia
#5
Ignacio Álvarez, Miquel Aguilar, Jose Manuel González, Montse Ysamat, Carles Lorenzo-Bosquet, Alvaro Alonso, Juan Pablo Tartari, Silvia Romero, Monica Diez-Fairen, Maria Carcel, Francisco Pujalte, Pau Pastor
BACKGROUND: Cerebrospinal fluid (CSF) biomarker studies have shown variable accuracy for diagnosis of Alzheimer's disease (AD); therefore, internal validation is recommended. OBJECTIVE: To investigate the correlation between CSF biomarkers and cerebral 18-Florbetapir positron emission tomography (Amyloid-PET) and calculate their sensitivity and specificity to obtain the optimal clinical cut-off points to diagnose the etiology of cognitive impairment. METHODS: We performed Amyloid-PET scans and CSF biomarker levels analyses in 68 subjects (50 with mild cognitive impairment, 11 with AD dementia, and 7 with non-AD dementia)...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154285/prediction-of-alzheimer-s-dementia-in-patients-with-amnestic-mild-cognitive-impairment-in-clinical-routine-incremental-value-of-biomarkers-of-neurodegeneration-and-brain-amyloidosis-added-stepwise-to-cognitive-status
#6
Catharina Lange, Per Suppa, Uwe Pietrzyk, Marcus R Makowski, Lothar Spies, Oliver Peters, Ralph Buchert
The aim of this study was to evaluate the incremental benefit of biomarkers for prediction of Alzheimer's disease dementia (ADD) in mild cognitive impairment (MCI) when added stepwise in the order of their collection in clinical routine. The model started with cognitive status characterized by the ADAS-13 score. Hippocampus volume (HV), cerebrospinal fluid (CSF) phospho-tau (pTau), and the FDG t-sum score in an AD-meta region-of-interest were compared as neurodegeneration markers. CSF-Aβ1-42 was used as amyloidosis marker...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154278/effects-of-physical-exercise-on-alzheimer-s-disease-biomarkers-a-systematic-review-of-intervention-studies
#7
Kristian Steen Frederiksen, Le Gjerum, Gunhild Waldemar, Steen Gregers Hasselbalch
Physical exercise may be an important adjunct to pharmacological treatment of Alzheimer's disease (AD). Animal studies indicate that exercise may be disease modifying through several mechanisms including reduction of AD pathology. We carried out a systematic review of intervention studies of physical exercise with hippocampal volume (on MRI), amyloid-β, total tau, phosphorylated tau in cerebrospinal fluid (CSF), 18F-FDG-PET or amyloid PET as outcome measures in healthy subjects, patients with subjective memory complaints, mild cognitive impairment, or AD...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154277/potential-of-low-dose-leuco-methylthioninium-bis-hydromethanesulphonate-lmtm-monotherapy-for-treatment-of-mild-alzheimer-s-disease-cohort-analysis-as-modified-primary-outcome-in-a-phase-iii-clinical-trial
#8
Gordon K Wilcock, Serge Gauthier, Giovanni B Frisoni, Jianping Jia, Jiri H Hardlund, Hans J Moebius, Peter Bentham, Karin A Kook, Bjoern O Schelter, Damon J Wischik, Charles S Davis, Roger T Staff, Vesna Vuksanovic, Trevor Ahearn, Luc Bracoud, Kohkan Shamsi, Ken Marek, John Seibyl, Gernot Riedel, John M D Storey, Charles R Harrington, Claude M Wischik
BACKGROUND: LMTM is being developed as a treatment for AD based on inhibition of tau aggregation. OBJECTIVES: To examine the efficacy of LMTM as monotherapy in non-randomized cohort analyses as modified primary outcomes in an 18-month Phase III trial in mild AD. METHODS: Mild AD patients (n = 800) were randomly assigned to 100 mg twice a day or 4 mg twice a day. Prior to unblinding, the Statistical Analysis Plan was revised to compare the 100 mg twice a day as monotherapy subgroup (n = 79) versus 4 mg twice a day as randomized (n = 396), and 4 mg twice a day as monotherapy (n = 76) versus 4 mg twice a day as add-on therapy (n = 297), with strong control of family-wise type I error...
November 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154275/association-of-cerebrospinal-fluid-csf-insulin-with-cognitive-performance-and-csf-biomarkers-of-alzheimer-s-disease
#9
Stefan L C Geijselaers, Pauline Aalten, Inez H G B Ramakers, Peter Paul De Deyn, Annemieke C Heijboer, Huiberdina L Koek, Marcel G M OldeRikkert, Janne M Papma, Fransje E Reesink, Lieke L Smits, Coen D A Stehouwer, Charlotte E Teunissen, Frans R J Verhey, Wiesje M van der Flier, Geert Jan Biessels
BACKGROUND: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD). OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype. METHODS: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154274/cognitive-decline-in-preclinical-alzheimer-s-disease-amyloid-beta-versus-tauopathy
#10
Colin M Huber, Connor Yee, Taylor May, Apoorva Dhanala, Cassie S Mitchell
 We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). "High" levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29154272/differences-in-synaptic-dysfunction-between-rtg4510-and-app-ps1-mouse-models-of-alzheimer-s-disease
#11
Simon Gelman, Jonathan Palma, Geoffrey Tombaugh, Afshin Ghavami
Genetically modified mice have provided insights into the progression and pathology of Alzheimer's disease (AD). Here, we have examined two mouse models of AD: the rTg4510 mouse, which overexpresses mutant human Tau gene, and the APP/PS1 mouse, which overexpresses mutant human genes for amyloid precursor protein and presenilin 1. Both models exhibit deficits in hippocampal function, but comparative analyses of these deficits are sparse. We used extracellular field potential recordings in hippocampal slices to study basal synaptic transmission (BST), paired-pulse facilitation (PPF), and long-term potentiation (LTP) at the Schaffer collateral-CA1 pyramidal cell synapses in both models...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29153990/cell-type-dependent-alzheimer-s-disease-phenotypes-probing-the-biology-of%C3%A2-selective-neuronal-vulnerability
#12
Christina R Muratore, Constance Zhou, Meichen Liao, Marty A Fernandez, Walter M Taylor, Valentina N Lagomarsino, Richard V Pearse, Heather C Rice, Joseph M Negri, Amy He, Priya Srikanth, Dana G Callahan, Taehwan Shin, Monica Zhou, David A Bennett, Scott Noggle, J Christopher Love, Dennis J Selkoe, Tracy L Young-Pearse
Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD...
November 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29153604/characterization-of-isolated-tau-reactive-antibodies-from-the-ivig-product-plasma-of-patients-with-alzheimer-s-disease-and-cognitively-normal-individuals
#13
Michala Krestova, Lenka Hromadkova, Zuzana Bilkova, Ales Bartos, Jan Ricny
The presence of natural tau-reactive antibodies was reported in human blood. In this study, we isolated and characterized natural tau-reactive antibodies occurring in IVIG product Flebogamma, plasma of patients with Alzheimer's disease (AD) and older cognitively normal persons (controls). Using blotting immunoassays and ELISA, we showed reactivity of antibodies obtained from IVIG and controls against a recombinant fragment of tau (155-421aa) and aggregates present in brains of AD patients. In contrast, antibodies isolated from plasma of AD patients reacted mainly with the recombinant full-length tau form and tau monomeric forms in brain tissue...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29151060/genetics-of-parkinson-s-disease-and-related-disorders
#14
REVIEW
Pei-Lan Zhang, Yan Chen, Chen-Hao Zhang, Yu-Xin Wang, Pedro Fernandez-Funez
Parkinson's disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum...
November 18, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29150549/psychometric-validation-of-the-needs-assessment-tool-progressive-disease-in-interstitial-lung-disease
#15
Miriam J Johnson, Armita Jamali, Joy Ross, Caroline Fairhurst, Jason Boland, Carla Reigada, Simon Paul Hart, Gunn Grande, David C Currow, Athol U Wells, Sabrina Bajwah, Thanos Papadopoulos, J Martin Bland, Janelle Yorke
The inter-rater/test-retest reliability and construct validity of a palliative care needs assessment tool in interstitial lung disease (NAT:PD-ILD) were tested using NAT:PD-ILD-guided video-recorded consultations, and NAT:PD-ILD-guided consultations, and patient and carer-report outcomes (St George's Respiratory Questionnaire (SGRQ)-ILD, Carer Strain Index (CSI)/Carer Support Needs Assessment Tool (CSNAT)). 11/16 items reached at least fair inter-rater agreement; 5 items reached at least moderate test-retest agreement...
November 17, 2017: Thorax
https://www.readbyqxmd.com/read/29148844/circadian-phase-circadian-period-and-chronotype-are-reproducible-over-months
#16
Thomas Kantermann, Charmane I Eastman
The timing of the circadian clock, circadian period and chronotype varies among individuals. To date, not much is known about how these parameters vary over time in an individual. We performed an analysis of the following five common circadian clock and chronotype measures: 1) the dim light melatonin onset (DLMO, a measure of circadian phase), 2) phase angle of entrainment (the phase the circadian clock assumes within the 24-h day, measured here as the interval between DLMO and bedtime/dark onset), 3) free-running circadian period (tau) from an ultradian forced desynchrony protocol (tau influences circadian phase and phase angle of entrainment), 4) mid-sleep on work-free days (MSF from the Munich ChronoType Questionnaire; MCTQ) and 5) the score from the Morningness-Eveningness Questionnaire (MEQ)...
November 17, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29148236/emerging-roles-of-er-stress-in-the-aetiology-and-pathogenesis-of-alzheimer-s-disease
#17
REVIEW
Yannis Gerakis, Claudio Hetz
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phophorylated Tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network is a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the Unfolded Protein Response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29147495/standardized-cannabis-sativa-extract-attenuates-tau-and-stathmin-gene-expression-in-the-melanoma-cell-line
#18
Golnaz Vaseghi, Mohamad Javad Taki, Shaghayegh Haghjooy Javanmard
Objectives: Metastasis is the main cause of death in patients with melanoma. Cannabis-based medicines are effective adjunctive drugs in cancer patients. Tau and Stathmin proteins are the key proteins in cancer metastasis. Here we have investigated the effect of a standardized Cannabis sativa extract on cell migration and Tau and Stathmin gene expression in the melanoma cell line. Materials and Methods: In the treatment group, melanoma (B1617) was treated 48 hr with various concentrations of standardized C...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29146293/andrographolide-a-promising-therapeutic-agent-negatively-regulates-glial-cell-derived-neurodegeneration-of-prefrontal-cortex-hippocampus-and-working-memory-impairment
#19
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29145658/characterization-of-detergent-insoluble-proteome-in-chronic-traumatic-encephalopathy
#20
Jonathan D Cherry, Ahmad Zeineddin, Eric B Dammer, James A Webster, Duc Duong, Nicholas T Seyfried, Allan I Levey, Victor E Alvarez, Bertrand R Huber, Thor D Stein, Patrick T Kiernan, Ann C McKee, James J Lah, Chadwick M Hales
Quantitative proteomics of postmortem human brain can identify dysfunctional proteins that contribute to neurodegenerative disorders like Alzheimer disease (AD) and frontotemporal dementia. Similar studies in chronic traumatic encephalopathy (CTE) are limited, therefore we hypothesized that proteomic sequencing of CTE frontal cortex brain homogenates from varying CTE pathologic stages may provide important new insights into this disorder. Quantitative proteomics of control, CTE and AD brains was performed to characterize differentially expressed proteins, and we identified over 4000 proteins in CTE brains, including significant enrichment of the microtubule associated protein tau...
November 14, 2017: Journal of Neuropathology and Experimental Neurology
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