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Alzheimers monitoring

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https://www.readbyqxmd.com/read/28534431/ameliorating-effect-of-anti-alzheimer-s-drugs-on-the-bidirectional-association-between-type-2-diabetes-mellitus-and-alzheimer-s-disease
#1
Amira S Ahmed, Rehab M Elgharabawy, Amal H Al-Najjar
Mild to severe forms of nervous system damage were exhibited by approximately 60-70% of diabetics. It is important to understand the association between type 2 diabetes mellitus and Alzheimer's disease. The aim of the present work is to understand the bidirectional association between type 2 diabetes and Alzheimer's disease pathogenesis, that was monitored by glycaemic status, lipid profile, amyloid beta 40 and 42 (Aβ40 and Aβ42), C-reactive protein, total creatine kinase, total lactate dehydrogenase, D-dimer and magnesium measurements, to assess the association between theses biochemical markers and each other, to estimate the possibility of utilizing the amyloid beta as biochemical marker of T2D in Alzheimer's patients, and to evaluate the effect of piracetam and memantine drugs on diabetes mellitus...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28531844/development-of-an-uplc-ms-ms-method-for-simultaneous-quantitation-of-11-d-amino-acids-in-different-regions-of-rat-brain-application-to-a-study-on-the-associations-of-d-amino-acid-concentration-changes-and-alzheimer-s-disease
#2
Zhe Li, Yuping Xing, Xingjie Guo, Yan Cui
There are significant differences in d-amino acid concentrations between healthy people and Alzheimer's disease patients. In order to investigate the potential correlation between d-amino acids and Alzheimer's disease, a simple and sensitive ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed. The method was applied to simultaneous determination of 11 d-amino acids in different regions of rat brain. Rat brain homogenates were firstly pretreated with protein precipitation procedure and then derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE]...
May 11, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28529627/-18-f-ge-180-pet-detects-reduced-microglia-activation-after-lm11a-31-therapy-in-a-mouse-model-of-alzheimer-s-disease
#3
Michelle L James, Nadia P Belichenko, Adam J Shuhendler, Aileen Hoehne, Lauren E Andrews, Christina Condon, Thuy-Vi V Nguyen, Vladimer Reiser, Paul Jones, William Trigg, Jianghong Rao, Sanjiv S Gambhir, Frank M Longo
Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo. Here we assessed flutriciclamide ([(18)F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [(18)F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining...
2017: Theranostics
https://www.readbyqxmd.com/read/28526935/diabetes-induced-abnormalities-of-mitochondrial-function-in-rat-brain-cortex-the-effect-of-n-3-fatty-acid-diet
#4
Maria Chomova, Maria Balazova, Jana Muchova
Diabetic encephalopathy, a proven complication of diabetes is associated with gradually developing end-organ damage in the CNS increasing the risk of stroke, cognitive dysfunction or Alzheimer's disease. This study investigated the response of rat cortical mitochondria to streptozotocin-induced diabetes and the potential for fish oil emulsion (FOE) to modulate mitochondrial function. Diabetes-induced deregulation of the respiratory chain function as a result of diminished complex I activity (CI) and cytochrome c oxidase hyperactivity was associated with attenuation of antioxidant defense of isolated cortical mitochondria, monitored by SOD activity, the thiol content, the dityrosine and protein-lipid peroxidation adduct formation...
May 19, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28523532/progressive-pathological-changes-in-neurochemical-profile-of-the-hippocampus-and-early-changes-in-the-olfactory-bulbs-of-tau-transgenic-mice-rtg4510
#5
Jieun Kim, In-Young Choi, Karen E Duff, Phil Lee
Tauopathies such as Alzheimer's disease and frontotemporal lobe degeneration (FTLD-tau) dementia, characterized by pathologic aggregation of the microtubule-associated tau protein and formation of neurofibrillary tangles, have been linked to neurodegeneration and cognitive decline. The early detection of cerebral abnormalities and the identification of biological contributors to the continuous pathologic processes of neurodegeneration in tauopathies critically hinge on sensitive and reliable measures of biomarkers in the living brain...
May 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28516240/in-vivo-pet-imaging-of-neuroinflammation-in-alzheimer-s-disease
#6
REVIEW
Julien Lagarde, Marie Sarazin, Michel Bottlaender
Increasing evidence suggests that neuroinflammation contributes to the pathophysiology of many neurodegenerative diseases, especially Alzheimer's disease (AD). Molecular imaging by PET may be a useful tool to assess neuroinflammation in vivo, thus helping to decipher the complex role of inflammatory processes in the pathophysiology of neurodegenerative diseases and providing a potential means of monitoring the effect of new therapeutic approaches. For this objective, the main target of PET studies is the 18 kDa translocator protein (TSPO), as it is overexpressed by activated microglia...
May 17, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28506742/investigation-of-gene-expression-and-serum-levels-of-pin1-and-enos-with-high-blood-pressure-in-patients-with-alzheimer-disease
#7
Mina Azimi, Masoud Nikanfar, Fatemeh Khakikhatibi, Reza Rahbarghazi, Seyed Manuchehr Nourazarian, Cigir Biray Avci, Alireza Nourazarian
According to evidence, Alzheimer's disease is known as one of the most serious neurodegenerative diseases, for which hypertension has been observed to be a key risk factor. Therefore, this study aims to examine the relationship between the PIN1 and eNOS genes expression, as well as serum levels and hypertension in Alzheimer's disease sufferers. Blood samples were obtained from subjects who were divided into four groups: the control group, normotensive Alzheimer's patients, the Alzheimer's sufferers group with hypertension, and the healthy group with only hypertension, considering the inhibition of confounding factors...
May 12, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28503250/localizing-sources-of-brain-disease-progression-with-network-diffusion-model
#8
Chenhui Hu, Xue Hua, Jun Ying, Paul M Thompson, Georges E Fakhri, Quanzheng Li
Pinpointing the sources of dementia is crucial to the effective treatment of neurodegenerative diseases. In this paper, we propose a diffusion model with impulsive sources over the brain connectivity network to model the progression of brain atrophy. To reliably estimate the atrophy sources, we impose sparse regularization on the source distribution and solve the inverse problem with an efficient gradient descent method. We localize the possible origins of Alzheimer's disease (AD) based on a large set of repeated magnetic resonance imaging (MRI) scans in Alzheimer's Disease Neuroimaging Initiative (ADNI) database...
October 2016: IEEE Journal of Selected Topics in Signal Processing
https://www.readbyqxmd.com/read/28503138/enhanced-feedback-related-negativity-in-alzheimer-s-disease
#9
Eri Nitta, Keiichi Onoda, Fuminori Ishitobi, Ryota Okazaki, Seiji Mishima, Atsushi Nagai, Shuhei Yamaguchi
Alzheimer's disease (AD), the most common cause of dementia in the elderly, results in the impairment of executive function, including that of performance monitoring. Feedback-related negativity (FRN) is an electrophysiological measure reflecting the activity of this monitoring system via feedback signals, and is generated from the anterior cingulate cortex. However, there have been no reports on FRN in AD. Based on prior aging studies, we hypothesized that FRN would decrease in AD patients. To assess this, FRN was measured in healthy individuals and those with AD during a simple gambling task involving positive and negative feedback stimuli...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28493068/cathepsin-s-increases-tau-oligomer-formation-through-limited-cleavage-but-only-il-6-not-cathespin-s-serum-levels-correlate-with-disease-severity-in-the-neurodegenerative-tauopathy-progressive-supranuclear-palsy
#10
Georg Nübling, M Schuberth, K Feldmer, A Giese, L M Holdt, D Teupser, S Lorenzl
Limited cleavage promotes the aggregation propensity of protein tau in neurodegenerative tauopathies. Cathepsin S (CatS) is overexpressed in brains of patients suffering from tauopathies such as Alzheimer's disease (AD). Furthermore, CatS serum levels correlate with survival in the elderly. The current study investigates whether limited cleavage by CatS promotes tau aggregation, and whether CatS serum levels may correlate with disease severity in tauopathies. Oligomer formation of fluorescently labeled protein tau was monitored by single particle fluorescence spectroscopy after coincubation with CatS...
May 10, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28490631/a-split-luciferase-complementation-real-time-reporting-assay-enables-monitoring-of-the-disease-associated-transmembrane-protein-trem2-in-live-cells
#11
Megan M Varnum, Kevin A Clayton, Asuka Yoshii-Kitahara, Grant Yonemoto, Lacin Koro, Seiko Ikezu, Tsuneya Ikezu
Triggering receptor expressed on myeloid cells 2 (TREM2) is a single transmembrane molecule uniquely expressed in microglia. TREM2 mutations are genetically linked to Nasu-Hakola disease and associated with multiple neurodegenerative disorders, including Alzheimer's disease (AD). TREM2 may regulate microglial inflammation and phagocytosis through coupling to the adaptor protein, TYRO protein tyrosine kinase binding protein (TYROBP). However, there is no functional system for monitoring this protein-protein interaction...
May 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28489317/pharmacogenomics-of-angiotensin-receptor-neprilysin-inhibitor-and-its-long-term-side-effects
#12
REVIEW
Chayakrit Krittanawong, Takeshi Kitai
The development of the promising agent sacubitril/valsartan, known as an angiotensin receptor blocker-neprilysin inhibitor (ARNI), to improve heart failure (HF) management, may benefit morbidity, mortality, and readmission rates in patients with HF. The PARADIGM-HF trial demonstrated that the ARNI can reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), while ongoing PARAMOUNT and PARAGON-HF trials determined whether the ARNI has morbidity and mortality benefits in patients with heart failure with preserved ejection fraction (HFpEF)...
May 10, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28488564/hippocampal-cholinergic-neurostimulating-peptide-as-a-possible-modulating-factor-against-glutamatergic-neuronal-disability-by-amyloid-oligomers
#13
Toyohiro Sato, Yoshiaki Ohi, Daisuke Kato, Masayuki Mizuno, Hiroshi Takase, Tetsuko Kanamori, Cesar V Borlongan, Akira Haji, Noriyuki Matsukawa
Despite having pathological changes in the brain associated Alzheimer's disease (AD), some patients have preserved cognitive function. A recent epidemiological study has shown that diet, exercise, cognitive training, and vascular risk monitoring interventions may reduce cognitive decline in at-risk elderly people in the general population. However, the details of molecular mechanisms underlying this cognitive function preservation are still unknown. Previous report demonstrated that enriched environments prevent the impairment of hippocampal long-term potentiation (LTP) through β2-adrenergic signals, when LTP is incompletely suppressed by synthetic amyloid-β (Aβ) oligomers...
May 9, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28485573/radiosynthesis-and-in-vivo-evaluation-of-11-c-a1070722-a-high-affinity-gsk-3-pet-tracer-in-primate-brain
#14
Jaya Prabhakaran, Francesca Zanderigo, Kiran Kumar Solingapuram Sai, Harry Rubin-Falcone, Matthew J Jorgensen, Jay R Kaplan, Akiva Mintz, J John Mann, J S Dileep Kumar
Dysfunction of glycogen synthase kinase 3 (GSK-3) is implicated in the etiology of Alzheimer's disease, Parkinson's disease, diabetes, pain, and cancer. A radiotracer for functional positron emission tomography (PET) imaging could be used to study the kinase in brain disorders and to facilitate the development of small molecule inhibitors of GSK-3 for treatment. At present, there is no target-specific or validated PET tracer available for the in vivo monitoring of GSK-3. We radiolabeled the small molecule inhibitor [(11)C]1-(7-methoxy- quinolin-4-yl)-3-(6-(trifluoromethyl)pyridin-2-yl)urea ([(11)C]A1070722) with high affinity to GSK-3 (Ki = 0...
May 17, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28477284/holocranohistochemistry-enables-the-visualization-of-%C3%AE-synuclein-expression-in-the-murine-olfactory-system-and-discovery-of-its-systemic-anti-microbial-effects
#15
Julianna J Tomlinson, Bojan Shutinoski, Li Dong, Fanyi Meng, Dina Elleithy, Nathalie A Lengacher, Angela P Nguyen, Greg O Cron, Qiubo Jiang, Erik D Roberson, Robert L Nussbaum, Nour K Majbour, Omar M El-Agnaf, Steffany A Bennett, Diane C Lagace, John M Woulfe, Subash Sad, Earl G Brown, Michael G Schlossmacher
Braak and Del Tredici have proposed that typical Parkinson disease (PD) has its origins in the olfactory bulb and gastrointestinal tract. However, the role of the olfactory system has insufficiently been explored in the pathogeneses of PD and Alzheimer disease (AD) in laboratory models. Here, we demonstrate applications of a new method to process mouse heads for microscopy by sectioning, mounting, and staining whole skulls ('holocranohistochemistry'). This technique permits the visualization of the olfactory system from the nasal cavity to mitral cells and dopamine-producing interneurons of glomeruli in the olfactory bulb...
May 5, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28476157/microglia-amplify-inflammatory-activation-of-astrocytes-in-manganese-neurotoxicity
#16
Kelly S Kirkley, Katriana A Popichak, Maryam F Afzali, Marie E Legare, Ronald B Tjalkens
BACKGROUND: As the primary immune response cell in the central nervous system, microglia constantly monitor the microenvironment and respond rapidly to stress, infection, and injury, making them important modulators of neuroinflammatory responses. In diseases such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and human immunodeficiency virus-induced dementia, activation of microglia precedes astrogliosis and overt neuronal loss. Although microgliosis is implicated in manganese (Mn) neurotoxicity, the role of microglia and glial crosstalk in Mn-induced neurodegeneration is poorly understood...
May 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28469554/physiological-functions-of-the-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-and-2
#17
REVIEW
Riqiang Yan
BACE1 was discovered as the β-secretase for initiating the cleavage of amyloid precursor protein (APP) at the β-secretase site, while its close homology BACE2 cleaves APP within the β-amyloid (Aβ) domain region and shows distinct cleavage preferences in vivo. Inhibition of BACE1 proteolytic activity has been confirmed to decrease Aβ generation and amyloid deposition, and thus specific inhibition of BACE1 by small molecules is a current focus for Alzheimer's disease therapy. While BACE1 inhibitors are being tested in advanced clinical trials, knowledge regarding the properties and physiological functions of BACE is highly important and this review summarizes advancements in BACE1 research over the past several years...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28461218/cerebrospinal-fluid-neurofilament-light-chain-as-a-biomarker-of-neurodegeneration-in-the-tg4510-and-mitopark-mouse-models
#18
Amalie Clement, Cathy Mitchelmore, Daniel R Andersson, Ayodeji A Asuni
A challenge in working with preclinical models of neurodegeneration has been how to non-invasively monitor disease progression. Neurofilament proteins are established axonal damage markers and have been found to be elevated in cerebrospinal fluid (CSF) and blood from patients with neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD) and tauopathies. We hypothesized that CSF neurofilament light (NF-L) can be used to track progression of neurodegeneration and potentially monitor the efficacy of novel therapeutic agents in preclinical development...
April 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/28451317/a-resorcinarene-for-inhibition-of-a%C3%AE-fibrillation
#19
Xu Han, Jiyong Park, Wei Wu, Andres Malagon, Lingyu Wang, Edgar Vargas, Athula Wikramanayake, K N Houk, Roger M Leblanc
Amyloid-β peptides (Aβ) fibrillation is the hallmark of Alzheimer's disease (AD). However, it has been challenging to discover potent agents in order to inhibit Aβ fibrillation. Herein, we demonstrated the effect of resorcinarene on inhibiting Aβ fibrillation in vitro via experimental and computational methods. Aβ were incubated with different concentrations of resorcinarene so as to monitor the kinetics by using thioflavin T binding assay. The results, which were further confirmed by far-UV CD spectroscopy and atomic force microscopy, strongly indicated that the higher concentration of resorcinarene, the more effective the inhibition of Aβ fibrillation...
March 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28445753/pyroglutamate-modified-amyloid-%C3%AE-3-42-shows-%C3%AE-helical-intermediates-before-amyloid-formation
#20
Christina Dammers, Kerstin Reiss, Lothar Gremer, Justin Lecher, Tamar Ziehm, Matthias Stoldt, Melanie Schwarten, Dieter Willbold
Pyroglutamate-modified amyloid-β (pEAβ) has been described as a relevant Aβ species in Alzheimer's-disease-affected brains, with pEAβ (3-42) as a dominant isoform. Aβ (1-40) and Aβ (1-42) have been well characterized under various solution conditions, including aqueous solutions containing trifluoroethanol (TFE). To characterize structural properties of pEAβ (3-42) possibly underlying its drastically increased aggregation propensity compared to Aβ (1-42), we started our studies in various TFE-water mixtures and found striking differences between the two Aβ species...
April 25, 2017: Biophysical Journal
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