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Alzheimers monitoring

Charlotte E Teunissen, Markus Otto, Sebastiaan Engelborghs, Sanna-Kaisa Herukka, Sylvain Lehmann, Piotr Lewczuk, Alberto Lleó, Armand Perret-Liaudet, Hayrettin Tumani, Martin R Turner, Marcel M Verbeek, Jens Wiltfang, Henrik Zetterberg, Lucilla Parnetti, Kaj Blennow
Body fluid biomarkers have great potential for different clinical purposes, including diagnosis, prognosis, patient stratification and treatment effect monitoring. This is exemplified by current use of several excellent biomarkers, such as the Alzheimer's disease cerebrospinal fluid (CSF) biomarkers, anti-neuromyelitis optica antibodies and blood neurofilament light. We still, however, have a strong need for additional biomarkers and several gaps in their development and implementation should be filled. Examples of such gaps are i) limited knowledge of the causes of neurological diseases, and thus hypotheses about the best biomarkers to detect subclinical stages of these diseases; ii) the limited success translating discoveries obtained by e...
March 15, 2018: Alzheimer's Research & Therapy
Elena Pérez-Ruiz, Deborah Decrop, Karen Ven, Lisa Tripodi, Karen Leirs, Joelle Rosseels, Marlies van de Wouwer, Nick Geukens, Ann De Vos, Eugeen Vanmechelen, Joris Winderickx, Jeroen Lammertyn, Dragana Spasic
The close correlation between Tau pathology and Alzheimer's disease (AD) progression makes this protein a suitable biomarker for diagnosis and monitoring of the disorder evolution. However, the use of Tau in diagnostics has been hampered, as it currently requires collection of cerebrospinal fluid (CSF), which is an invasive clinical procedure. Although measuring Tau-levels in blood plasma would be favorable, the concentrations are below the detection limit of a conventional ELISA. In this work, we developed a digital ELISA for the quantification of attomolar protein Tau concentrations in both buffer and biological samples...
July 26, 2018: Analytica Chimica Acta
Miriam A Kael, Daniel K Weber, Frances Separovic, Marc-Antoine Sani
The cleavage of the amyloid precursor protein by β- and γ-secretases is a key event in Alzheimer's disease. A fusion protein was constructed to investigate the cleavage rate and aggregation kinetics of amyloid-beta (1-40) (Aβ(1-40)) peptides. The peptide was expressed with a Small Ubiquitin-Like Modifier (SUMO) on the N-terminus and cleaved by a SUMO protease Ulp1. The time course of the cleavage reaction was monitored by SDS-PAGE gel with 100:1 or 1000:1 SUMO-Aβ(1-40) to Ulp1 molar ratio and in the presence of brain total lipid extract unilamellar vesicles...
March 8, 2018: Biochimica et Biophysica Acta
Alanna Sedgwick, M Olivia Balmert, Crislyn D'Souza-Schorey
Aberrant cellular cholesterol accumulation contributes to the pathophysiology of many diseases including neurodegenerative disorders such as Niemann-Pick Type C (NPC) and Alzheimer's Disease1-4 . Many aspects of cholesterol efflux from cells remain elusive. Here we describe the utility of cholesterol-rich giant plasma membrane vesicles (GPMVs) as a means to monitor cholesterol that is translocated to the plasma membrane for secretion. We demonstrate that small molecules known to enhance lipid efflux, including those in clinical trials for lipid storage disorders, enhance this GPMV formation...
March 6, 2018: Experimental Cell Research
Silvia Chapman, Leigh E Colvin, Matti Vuorre, Gianna Cocchini, Janet Metcalfe, Edward D Huey, Stephanie Cosentino
Anosognosia for memory loss is a common feature of Alzheimer's disease (AD). Recent theories have proposed that anosognosia, a disruption in awareness at a global level, may reflect specific deficits in self-monitoring, or local awareness. Though anosognosia for memory loss has been shown to relate to memory self-monitoring, it is not clear if it relates to self-monitoring deficits in other domains (i.e., motor). The current study examined this question by analyzing the relationship between anosognosia for memory loss, memory monitoring, and motor monitoring in 35 individuals with mild to moderate AD...
February 8, 2018: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Lisa-Maria Needham, Judith Weber, James W B Fyfe, Omaru M Kabia, Dung T Do, Ewa Klimont, Yu Zhang, Margarida Rodrigues, Christopher M Dobson, Sonia Ghandi, Sarah E Bohndiek, Thomas N Snaddon, Steven F Lee
Protein aggregation into amyloid deposits and oxidative stress are key features of many neurodegenerative disorders including Parkinson's and Alzheimer's disease. We report here the creation of four highly sensitive bifunctional fluorescent probes, capable of H2 O2 and/or amyloid aggregate detection. These bifunctional sensors use a benzothiazole core for amyloid localization and boronic ester oxidation to specifically detect H2 O2 . We characterized the optical properties of these probes using both bulk fluorescence measurements and single-aggregate fluorescence imaging, and quantify changes in their fluorescence properties upon addition of amyloid aggregates of α-synuclein and pathophysiological H2 O2 concentrations...
February 2018: Royal Society Open Science
Cornelius K Donat, Nazanin Mirzaei, Sac-Pharm Tang, Paul Edison, Magdalena Sastre
Deficits in neuronal function and synaptic plasticity in Alzheimer's disease (AD) are believed to be linked to microglial activation. A hallmark of reactive microglia is the upregulation of mitochondrial translocator protein (TSPO) expression. Positron emission tomography (PET) is a nuclear imaging technique that measures the distribution of trace doses of radiolabeled compounds in the body over time. PET imaging using the 2nd generation TSPO tracer [11 C]PBR28 provides an opportunity for accurate visualization and quantification of changes in microglial density in transgenic mouse models of Alzheimer's disease (AD)...
2018: Methods in Molecular Biology
Frank J Wolters, M Arfan Ikram
Dementia is among the leading causes of death and disability. Due to the ageing population, its prevalence is expected to nearly triple worldwide by 2050, urging the development of preventive and curative interventions. Various modifiable risk factors have been identified in community-based cohort studies, but insight into the underlying pathophysiological mechanisms is lacking. Clinical trials have thus far failed in the development of disease-modifying therapy in patients with dementia, thereby triggering a shift of focus toward the presymptomatic phase of disease...
2018: Methods in Molecular Biology
John Grundy, Kon Mouzakis, Rajesh Vasa, Andrew Cain, Maheswaree Curumsing, Mohamed Abdelrazek, Niroshine Fernando
By the 2050, it is estimated that the proportion of people over the age of 80 will have risen from 3.9% to 9.1% of population of Organisation for Economic Cooperation and Development countries. A large proportion of these people will need significant help to manage various chronic illnesses, including dementia, heart disease, diabetes, limited physical movement and many others. Current approaches typically focus on acute episodes of illness and are not well designed to provide adequately for daily living care support...
2018: Studies in Health Technology and Informatics
Lauren L Mitchell, Colleen M Peterson, Shaina R Rud, Eric Jutkowitz, Andrielle Sarkinen, Sierra Trost, Carolyn M Porta, Jessica M Finlay, Joseph E Gaugler
Technologies have emerged that aim to help older persons with Alzheimer's disease and related dementias (ADRDs) remain at home while also supporting their caregiving family members. However, the usefulness of these innovations, particularly in home-based care contexts, remains underexplored. The current study evaluated the acceptability and utility of an in-home remote activity monitoring (RAM) system for 30 family caregivers of persons with ADRD via quantitative survey data collected over a 6-month period and qualitative survey and interview data collected for up to 18 months...
March 1, 2018: Journal of Applied Gerontology: the Official Journal of the Southern Gerontological Society
Qiu-Lan Ma, Edmond Teng, Xiaohong Zuo, Mychica Jones, Bruce Teter, Evan Y Zhao, Cansheng Zhu, Tina Bilousova, Karen H Gylys, Liana G Apostolova, Mary Jo LaDu, Mir Ahamed Hossain, Sally A Frautschy, Gregory M Cole
Synaptic neurodegeneration is thought to be an early event initiated by soluble β-amyloid (Aβ) aggregates that closely correlates with cognitive decline in Alzheimer disease (AD). Apolipoprotein ε4 (APOE4) is the most common genetic risk factor for both familial AD (FAD) and sporadic AD; it accelerates Aβ aggregation and selectively impairs glutamate receptor function and synaptic plasticity. However, its molecular mechanisms remain elusive and these synaptic deficits are difficult to monitor. AD- and APOE4-dependent plasma biomarkers have been proposed, but synapse-related plasma biomarkers are lacking...
February 28, 2018: Neurobiology of Disease
Mohammad Khursheed Siddiqi, Parvez Alam, Sumit Kumar Chaturvedi, Mohsin Vahid Khan, Saima Nusrat, Sadia Malik, Rizwan Hasan Khan
Protein aggregation and amyloid fibrillation are responsible for several serious pathological conditions (like type II diabetes, Alzheimer's and Parkinson's diseases etc.) and protein drugs ineffectiveness. Therefore, a molecule that can inhibit the amyloid fibrillation and potentially clear amyloid fibrils is of great therapeutic value. In this manuscript, we investigated the antiamyloidogenic, fibril disaggregating, as well as cell protective effect of an anti-tuberculosis drug, Capreomycin (CN). Aggregation kinetics data, as monitored by ThT fluorescence, inferred that CN retards the insulin amyloid fibrillation by primarily targeting the fibril elongation step with little effect on lag time...
February 26, 2018: Biochimica et Biophysica Acta
Laura Bonfili, Valentina Cecarini, Massimiliano Cuccioloni, Mauro Angeletti, Sara Berardi, Silvia Scarpona, Giacomo Rossi, Anna Maria Eleuteri
The gut-brain axis is a bidirectional communication network functionally linking the gut and the central nervous system (CNS). Based on this, the rational manipulation of intestinal microbiota represents a novel attractive therapeutic strategy for the treatment of CNS-associated disorders. In this study, we explored the properties of a probiotic formulation (namely SLAB51) in counteracting brain oxidative damages associated with Alzheimer's disease (AD). Specifically, transgenic AD mice (3xTg-AD) were treated with SLAB51 and the effects on protein oxidation, neuronal antioxidant defence and repair systems were monitored, with the particular focus on the role of SIRT1-related pathways...
February 28, 2018: Molecular Neurobiology
Concetta Di Natale, Alessandra Monaco, Carlo Pedone, Alessandro Tessitore, Antonio De Mase, Gioacchino Tedeschi, Paolo Antonio Netti, Paolo Abrescia
24-hydroxycholesterol (24OH-C) is synthesized almost exclusively in neurons. This oxysterol is mostly present as ester form in both cerebrospinal fluid and plasma. The enzyme lecithin-cholesterol acyltransferase esterifies 24OH-C in the brain, and the level of 24OH-C esters in cerebrospinal fluid was found to be correlated with the level of 24OH-C esters in plasma. Decreased levels of 24OH-C esters levels were previously found in Alzheimer's disease and Amyotrophic Lateral Sclerosis. This finding was attributed to the inhibitory effect of oxidative stress on lecithin-cholesterol acyltransferase activity in neurodegenerative conditions...
February 24, 2018: Neuroscience Letters
Frederic Brosseron, Andreas Traschütz, Catherine N Widmann, Markus P Kummer, Pawel Tacik, Francesco Santarelli, Frank Jessen, Michael T Heneka
BACKGROUND: Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this study, we sought to clarify the utility of inflammatory biomarkers in diagnostic procedures of AD in three steps: (1) to screen for proteins that are robustly detectable in cerebrospinal fluid; (2) based on this analysis, to explore any associations between the analytically robust markers and salient pathological features of AD; and (3) to determine the discriminative power of these markers in the clinical diagnosis of AD...
February 26, 2018: Alzheimer's Research & Therapy
Claudia Marinangeli, Jérome Kluza, Philippe Marchetti, Luc Buée, Valérie Vingtdeux
AMP-activated protein kinase (AMPK) is the intracellular master energy sensor and metabolic regulator. AMPK is involved in cell energy homeostasis through the regulation of glycolytic flux and mitochondrial biogenesis. Interestingly, metabolic dysfunctions and AMPK deregulations are observed in many neurodegenerative diseases, including Alzheimer's. While these deregulations could play a key role in the development of these diseases, the study of metabolic fluxes has remained quite challenging and time-consuming...
2018: Methods in Molecular Biology
Wei Zhang, Yi Guo, Bo Li, Qi Zhang, Jian-Hui Liu, Guo-Jun Gu, Jin-Hong Wang, Rui-Kang Bao, Yu-Jie Chen, Jian-Rong Xu
Cerebral amyloid angiopathy (CAA) is present in up to 90% of patients with Alzheimer's disease (AD), and may interact with classical neuropathology to exacerbate cognitive decline. Since growth differentiation factor 11 (GDF11) can activate vascular remodeling, we tested its effects on cognitive function and neuroinflammatory changes of AD model mice. We intravenously administered GDF11 or vehicle daily to 12-month-old transgenic mice overexpressing the amyloid-β protein precursor (AβPP)/PS1). Cognitive function was monitored using the Morris water maze, and after conclusion of the treatment, we assessed the morphology and presence of inflammatory markers in the cerebral vasculature...
2018: Journal of Alzheimer's Disease: JAD
Ran Furman, Jin V Lee, Paul H Axelsen
The quantitative analysis of polyunsaturated fatty acyl (PUFA) chain oxidation products in tissue samples by mass spectrometry is hindered by the lack of durable internal standards for the large number of possible products. To address this problem in a study of oxidative PUFA degradation in Alzheimer's disease (AD) brain, uniformly13 C-labeled arachidonic acid (ARA) was produced biosynthetically, and allowed to oxidize under controlled conditions into a mixture of U-13 C-labeled ARA oxidation products. The components of this mixture were characterized with respect to their partitioning behavior during lipid extraction, their durability during saponification, trends in mouse brain tissue concentrations during post mortem intervals, and their overall suitability as internal standards for multiple-reaction monitoring tandem mass spectrometry...
February 21, 2018: Free Radical Biology & Medicine
Victor L Villemagne, Vincent Doré, Samantha C Burnham, Colin L Masters, Christopher C Rowe
Most neurodegenerative disorders are associated with aggregated protein deposits. In the case of Alzheimer disease (AD), extracellular amyloid-β (Aβ) aggregates and intracellular tau neurofibrillary tangles are the two neuropathological hallmarks of the disease. Aβ-PET imaging has already been approved for clinical use and is being used in clinical trials of anti-Aβ therapies both for patient recruitment and as an outcome measure. These studies have shown that Aβ accumulation is a protracted process that can extend for more than 2 decades before the onset of clinical AD...
February 16, 2018: Nature Reviews. Neurology
Vo Van Giau, Hyon Lee, Kyu Hwan Shim, Eva Bagyinszky, Seong Soo A An
Genetic variations play an important role in the clinical presentation and progression of Alzheimer's disease (AD), especially early-onset Alzheimer's disease. Hundreds of mutations have been reported with the majority resulting from alterations in β-amyloid precursor protein ( APP ), presenilin 1 ( PSEN1 ), or presenilin 2 ( PSEN2 ) genes. The roles of these mutations in the pathogenesis of AD have been classically confirmed or refuted through functional studies, where the mutations are cloned, inserted into cell lines, and monitored for changes in various properties including cell survival, amyloid production, or Aβ42/40 ratio...
2018: Clinical Interventions in Aging
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