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Alzheimers disease treatment

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https://www.readbyqxmd.com/read/29353102/aging-african-green-monkeys-manifest-transcriptional-pathological-and-cognitive-hallmarks-of-human-alzheimer-s-disease
#1
Paige E Cramer, Renee C Gentzel, Keith Q Tanis, Joshua Vardigan, Yi Wang, Brett Connolly, Philip Manfre, Kenneth Lodge, John J Renger, Celina Zerbinatti, Jason M Uslaner
While many preclinical models of Alzheimer's disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in 2 higher order species, the African green monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29353101/amyloid-pathology-in-the-progression-to-mild-cognitive-impairment
#2
Philip S Insel, Oskar Hansson, R Scott Mackin, Michael Weiner, Niklas Mattsson
The objective of this study was to determine the cognitive and functional decline and development of brain injury in individuals progressing from preclinical (β-amyloid positive cognitively normal) to prodromal Alzheimer's disease (AD) (β-amyloid positive mild cognitive impairment [MCI]), and compare this with individuals who progress to MCI in the absence of significant amyloid pathology. Seventy-five cognitively healthy participants who progressed to MCI were followed for 4 years on average and up to 10 years...
December 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29353052/evidence-for-altered-insulin-receptor-signaling-in-alzheimer-s-disease
#3
REVIEW
Chelsea M Griffith, Tore Eid, Gregory M Rose, Peter R Patrylo
Epidemiological data have shown that metabolic disease can increase the propensity for developing cognitive decline and dementia, particularly Alzheimer's disease (AD). While this interaction is not completely understood, clinical studies suggest that both hyper- and hypoinsulinemia are associated with an increased risk for developing AD. Indeed, insulin signaling is altered in post-mortem brain tissue from AD patients and treatments known to enhance insulin signaling, can improve cognitive function. Further, clinical evidence has shown that AD patients and mouse models of AD often display alterations in peripheral metabolism...
January 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29352978/use-of-multimodality-imaging-and-artificial-intelligence-for-diagnosis-and-prognosis-of-early-stages-of-alzheimer-s-disease
#4
REVIEW
Xiaonan Liu, Kewei Chen, Teresa Wu, David Weidman, Fleming Lure, Jing Li
Alzheimer's disease (AD) is a major neurodegenerative disease and the most common cause of dementia. Currently, no treatment exists to slow down or stop the progression of AD. There is converging belief that disease-modifying treatments should focus on early stages of the disease, that is, the mild cognitive impairment (MCI) and preclinical stages. Making a diagnosis of AD and offering a prognosis (likelihood of converting to AD) at these early stages are challenging tasks but possible with the help of multimodality imaging, such as magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission topography (PET), amyloid-PET, and recently introduced tau-PET, which provides different but complementary information...
January 10, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29352507/nuclear-and-membrane-estrogen-receptor-antagonists-induce-similar-mtorc2-activation-reversible-changes-in-synaptic-protein-expression-and-actin-polymerization-in-the-mouse-hippocampus
#5
Fang-Zhou Xing, Yan-Gang Zhao, Yuan-Yuan Zhang, Li He, Ji-Kai Zhao, Meng-Ying Liu, Yan Liu, Ji-Qiang Zhang
AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is unclear. METHODS: We treated animals with nER antagonists (MPP/PHTPP) or the mER antagonist (G15) alone or in combination with A-443654, an activator of mTORC2...
January 19, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29351469/inhibition-of-mtor-protects-the-blood-brain-barrier-in-models-of-alzheimer-s-disease-and-vascular-cognitive-impairment
#6
Candice E Van Skike, Jordan B Jahrling, Angela B Olson, Naomi L Sayre, Stacy A Hussong, Zoltan I Ungvari, James D Lechleiter, Veronica Galvan
An intact blood-brain barrier (BBB) limits entry of pro-inflammatory and neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in Alzheimer's disease (AD), which contributes significantly to the progression of AD pathologies and cognitive decline. However, the mechanisms underlying BBB breakdown in AD remain elusive and no interventions are available for treatment or prevention. We and others recently established that inhibition of the mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields significant neuroprotective effects, improving cerebrovascular and cognitive function in mouse models of AD...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29350764/the-protective-effect-of-antarctic-krill-oil-on-cognitive-function-by-inhibiting-oxidative-stress-in-the-brain-of-senescence-accelerated-prone-mouse-strain-8-samp8-mice
#7
Qian Li, Fengjuan Wu, Min Wen, Teruyoshi Yanagita, Changhu Xue, Tiantian Zhang, Yuming Wang
Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative stress plays a vital role in its progression. Antarctic krill oil (AKO) is rich in polyunsaturated fatty acids, which has various biological activities, such as improving insulin sensitivity, alleviating inflammation and ameliorating oxidative stress. In this study, the protective effect of AKO against AD were investigated in senescence-accelerated prone mouse strain 8 (SAMP8) mice. Results showed that treatment with AKO could effectively ameliorate learning and memory deficits and ease the anxiety in SAMP8 mice by Morris water maze, Barnes maze test and open-field test...
January 19, 2018: Journal of Food Science
https://www.readbyqxmd.com/read/29350177/antidepressant-medication-in-a-german-cohort-of-patients-with-alzheimer-s-disease%C3%A2
#8
Philipp Hessmann, Richard Dodel, Erika Baum, Matthias J Müller, Greta Paschke, Bernhard Kis, Jan Zeidler, Mike Klora, Jens-Peter Reese, Monika Balzer-Geldsetzer
OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29349578/in-situ-tissue-labeling-of-cerebral-amyloid-using-hiv-related-tat-peptide
#9
E Maderna, L Colombo, A Cagnotto, G Di Fede, A Indaco, F Tagliavini, M Salmona, G Giaccone
Delivering peptide-based drugs to the brain is a major challenge because of the existence of the blood-brain barrier (BBB). To overcome this problem, cell-penetrating peptides derived from proteins that are able to cross biological membranes have been used as cell-permeable and brain-penetrant compounds. An example is the transactivator of transcription protein transduction domain (Tat) of the human immunodeficiency virus. The basic domain of Tat is formed of arginine and lysine amino acid residues. Tat has been used as brain-penetrant carrier also in therapies for Alzheimer disease (AD), the most common form of dementia characterized by extracellular cerebral deposits of amyloid made up of Aβ peptide...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29349349/a-retrospective-analysis-of-outpatient-anesthesia-management-for-dental-treatment-of-patients-with-severe-alzheimer-s-disease
#10
Eunsun So, Hyun Jeong Kim, Myong-Hwan Karm, Kwang-Suk Seo, Juhea Chang, Joo Hyung Lee
Background: The number of patients with Alzheimer's disease is growing worldwide, and the proportion of patients requiring dental treatment under general anesthesia increases with increasing severity of the disease. However, outpatient anesthesia management for these patients involves great risks, as most patients with Alzheimer's disease are old and may show reduced cardiopulmonary functions and have cognitive disorders. Methods: This study retrospectively investigated 43 patients with Alzheimer's disease who received outpatient anesthesia for dental treatment between 2012-2017...
December 2017: Journal of Dental Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/29348604/cromolyn-reduces-levels-of-the-alzheimer-s-disease-associated-amyloid-%C3%AE-protein-by-promoting-microglial-phagocytosis
#11
Can Zhang, Ana Griciuc, Eloise Hudry, Yu Wan, Luisa Quinti, Joseph Ward, Angela M Forte, Xunuo Shen, ChongZhao Ran, David R Elmaleh, Rudolph E Tanzi
Amyloid-beta protein (Aβ) deposition is a pathological hallmark of Alzheimer's disease (AD). Aβ deposition triggers both pro-neuroinflammatory microglial activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma therapeutic agent previously shown to reduce Aβ levels in transgenic AD mouse brains after one-week of treatment. Here, we further explored these effects as well as the mechanism of action of cromolyn, alone, and in combination with ibuprofen in APPSwedish-expressing Tg2576 mice...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348391/effects-of-senescence-and-angiotensin-ii-on-expression-and-processing-of-amyloid-precursor-protein-in-human-cerebral-microvascular-endothelial-cells
#12
Ruohan Sun, Tongrong He, Yujun Pan, Zvonimir S Katusic
The present study was designed to determine the effects of senescence and angiotensin II (Ang II) on expression and processing of amyloid precursor protein (APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a decrease in APP expression thereby resulting in reduced secretion of soluble APPα (sAPPα). In contrast, β-site APP cleaving enzyme (BACE1) expression and production of amyloid β (Aβ)40 were increased in senescent endothelium. Importantly, in senescent human BMECs, treatment with BACE1 inhibitor IV inhibited Aβ generation and increased sAPPα production by enhancing a disintegrin and metalloprotease (ADAM)10 expression...
January 15, 2018: Aging
https://www.readbyqxmd.com/read/29347996/the-apathy-in-dementia-methylphenidate-trial-2-admet-2-study-protocol-for-a-randomized-controlled-trial
#13
Roberta W Scherer, Lea Drye, Jacobo Mintzer, Krista Lanctôt, Paul Rosenberg, Nathan Herrmann, Prasad Padala, Olga Brawman-Mintzer, William Burke, Suzanne Craft, Alan J Lerner, Allan Levey, Anton Porsteinsson, Christopher H van Dyck
BACKGROUND: Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events...
January 18, 2018: Trials
https://www.readbyqxmd.com/read/29346315/dietary-total-prenylflavonoids-from-the-fruits-of-psoralea-corylifolia-l-prevents-age-related-cognitive-deficits-and-down-regulates-alzheimer-s-markers-in-samp8-mice
#14
Zhi-Jing Chen, Yan-Fang Yang, Ying-Tao Zhang, Dong-Hui Yang
Alzheimer's disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29346273/report-on-the-symposium-molecular-mechanisms-involved-in-neurodegeneration
#15
Giselle Pentón-Rol, Majel Cervantes-Llanos
The prevalence of neurodegenerative diseases is currently a major concern in public health because of the lack of neuroprotective and neuroregenerative drugs. The symposium on Molecular Mechanisms Involved in Neurodegeneration held in Varadero, Cuba, updated the participants on the basic mechanisms of neurodegeneration, on the different approaches for drug discovery, and on early research results on therapeutic approaches for the treatment of neurodegenerative diseases. Alzheimer's disease and in silico research were covered by many of the presentations in the symposium, under the umbrella of the "State of the Art of Non-clinical Models for Neurodegenerative Diseases" International Congress, held from 20 to 24 June 2017...
January 18, 2018: Behavioral Sciences
https://www.readbyqxmd.com/read/29345897/design-synthesis-and-biological-evaluation-of-1-benzylamino-2-hydroxyalkyl-derivatives-as-new-potential-disease-modifying-multifunctional-anti-alzheimer-s-agents
#16
Dawid Panek, Anna Więckowska, Jakub Jończyk, Justyna Godyń, Marek W Bajda, Tomasz Wichur, Anna Pasieka, Damijan Knez, Anja Pislar, Jan Korabecny, Ondrej Soukup, Vendula Sepsova, Raimon Sabaté, Janko Kos, Stanislav Gobec, Barbara Malawska
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, β-secretase, β-amyloid and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets - inhibition of β-secretase (IC50 hBACE-1 = 41...
January 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29345437/antioxidant-and-acetylcholinesterase-inhibitory-activities-of-ginger-root-zingiber-officinale-roscoe-extract
#17
Bui Thanh Tung, Dang Kim Thu, Nguyen Thi Kim Thu, Nguyen Thanh Hai
Background Zingiber officinale Roscoe has been used in traditional medicine for the treatment of neurological disorder. This study aimed to investigate the phenolic contents, antioxidant, acetylcholinesterase enzyme (AChE) inhibitory activities of different fraction of Z. officinale root grown in Vietnam. Methods The roots of Z. officinale are extracted with ethanol 96 % and fractionated with n-hexane, ethyl acetate (EtOAc) and butanol (BuOH) solvents. These fractions evaluated the antioxidant activity by 1,1-Diphenyl -2-picrylhydrazyl (DPPH) assay and AChE inhibitory activity by Ellman's colorimetric method...
May 4, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/29344418/advances-in-the-studies-of-ginkgo-biloba-leaves-extract-on-aging-related-diseases
#18
REVIEW
Wei Zuo, Feng Yan, Bo Zhang, Jiantao Li, Dan Mei
The prevalence of degenerative disorders in public health has promoted in-depth investigations of the underlying pathogenesis and the development of new treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo biloba leaves and has been used for thousands of years. In recent decades, both basic and clinical studies have established the effects of EGb. It is widely used in various degenerative diseases such as cerebrovascular disease, Alzheimer's disease, macroangiopathy and more. Here, we reviewed several pharmacological mechanisms of EGb, including its antioxidant properties, prevention of mitochondrial dysfunctions, and effect on apoptosis...
December 2017: Aging and Disease
https://www.readbyqxmd.com/read/29343976/epidemiology-associated-burden-and-current-clinical-practice-for-the-diagnosis-and-management-of-alzheimer-s-disease-in-japan
#19
REVIEW
William Montgomery, Kaname Ueda, Margaret Jorgensen, Shari Stathis, Yuanyuan Cheng, Tomomi Nakamura
The burden of dementia in Japan is large and growing. With the world's fastest aging population, it is estimated that one in five elderly people will be living with dementia in Japan by 2025. The most common form of dementia is Alzheimer's disease (AD), accounting for around two-thirds of dementia cases. A systematic review was conducted to examine the epidemiology and associated burden of AD in Japan and to identify how AD is diagnosed and managed in Japan. English and Japanese language databases were searched for articles published between January 2000 and November 2015...
2018: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/29341888/protection-against-the-neurotoxic-effects-of-%C3%AE-amyloid-peptide-on-cultured-neuronal-cells-by-lovastatin-involves-elevated-expression-of-%C3%AE-7-nicotinic-acetylcholine-receptors-and-activating-phosphorylation-of-protein-kinases
#20
Liang Zhao, Yan Xiao, Jin Xiu, Long-Chun Tan, Zhi-Zhong Guan
The treatment of neurodegenerative diseases with statins has drawn increasing attention, but the related molecular mechanisms remain elusive. To examine the pleiotropic cholesterol-independent effects of statins in connection with the treatment of Alzheimer disease, we probed the influence of lovastatin on the metabolism of amyloid precursor protein (APP) , expression of nicotinic acetylcholine receptors (nAChRs), and activity of mitogen-activated protein kinase in primary cultured neurons and SH-SY5Y cells over-expressing human APP670/671...
January 13, 2018: American Journal of Pathology
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