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Alzheimers disease treatment

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https://www.readbyqxmd.com/read/28453490/plasma-amyloid-%C3%AE-and-alzheimer-s-disease-related-changes-in-late-life-depression
#1
Chiemi Yamazaki, Toshio Tamaoki, Akihiko Nunomura, Kenichi Tamai, Kazuyuki Yasuda, Nobutaka Motohashi
To elucidate an involvement of amyloid dysmetabolism in the pathophysiology of depression, we investigated associations of plasma amyloid-β (Aβ) levels with Alzheimer's disease-related changes in neuroimaging and cognitive dysfunction in patients with late-life depression. Higher plasma Aβ40, but not Aβ42 nor Aβ40/Aβ42 ratio, was associated with higher degree of parahippocampal atrophy and lower verbal fluency performance. Indeed, high plasma Aβ40 predicted poor cognitive prognosis of depressed patients with mild cognitive impairment...
April 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453483/remyelination-a-potential-therapeutic-strategy-for-alzheimer-s-disease
#2
Junjun Sun, Hong Zhou, Feng Bai, Zhijun Zhang, Qingguo Ren
Myelin is a lipid-rich multilamellar membrane that wraps around long segments of neuronal axons and it increases the conduction of action potentials, transports the necessary trophic support to the neuronal axons, and reduces the energy consumed by the neuronal axons. Together with axons, myelin is a prerequisite for the higher functions of the central nervous system and complex forms of network integration. Myelin impairments have been suggested to lead to neuronal dysfunction and cognitive decline. Accumulating evidence, including brain imaging and postmortem and genetic association studies, has implicated myelin impairments in Alzheimer's disease (AD)...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453480/a-multifunctional-biocompatible-drug-candidate-is-highly-effective-in-delaying-pathological-signs-of-alzheimer-s-disease-in-5xfad-mice
#3
Hadar Segal-Gavish, Ortal Danino, Yael Barhum, Tali Ben-Zur, Ella Shai, David Varon, Daniel Offen, Bilha Fischer
BACKGROUND: Metal-ion-chelation was suggested to prevent zinc and copper ions-induced amyloid-β (Aβ) aggregation and oxidative stress, both implicated in the pathophysiology of Alzheimer's disease (AD). In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we previously tested a series of nucleoside 5'-phosphorothioate derivatives as agents for decomposition of Cu(I)/Cu(II)/Zn(II)-Aβ-aggregates, and as inhibitors of OH radicals formation in Cu(I) or Fe(II) /H2O2 solution...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453473/prodromal-dementia-with-lewy-bodies-and-prodromal-alzheimer-s-disease-a-comparison-of-the-cognitive-and-clinical-profiles
#4
Dilman Sadiq, Tim Whitfield, Lean Lee, Tim Stevens, Sergi Costafreda, Zuzana Walker
BACKGROUND: Dementia must be diagnosed accurately and early in the disease course to allow pathology-specific treatments to be effective. Dementia with Lewy bodies (DLB) is often misdiagnosed as Alzheimer's disease (AD), especially at the prodromal stage. OBJECTIVE: To compare the clinical and neuropsychological profiles of mild cognitive impairment (MCI) patients who, at follow-up, progressed to AD (retrospectively AD-MCI) or DLB (retrospectively DLB-MCI) or remained MCI...
April 28, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453471/a-randomized-double-blind-placebo-controlled-phase-ii-study-of-oral-elnd005-scyllo-inositol-in-young-adults-with-down-syndrome-without-dementia
#5
Michael S Rafii, Brian G Skotko, Mary Ellen McDonough, Margaret Pulsifer, Casey Evans, Eric Doran, Gabriela Muranevici, Patrick Kesslak, Susan Abushakra, Ira T Lott
BACKGROUND: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. OBJECTIVE: To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia...
April 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28453469/use-of-analgesics-opioids-and-nonsteroidal-anti-inflammatory-drugs-and-dementia-related-neuropathology-in-a-community-based-autopsy-cohort
#6
Sascha Dublin, Rod L Walker, Shelly L Gray, Rebecca A Hubbard, Melissa L Anderson, Onchee Yu, Thomas J Montine, Paul K Crane, Josh A Sonnen, Eric B Larson
BACKGROUND: Opioids may influence the development of Alzheimer's disease (AD). Some studies have observed AD pathology in the brains of opioid abusers. No study has examined the association between prescription opioid use and dementia-related neuropathologic changes. OBJECTIVE: To examine the relationship between prescription opioid or NSAID use and dementia-related neuropathologic changes. METHODS: Within a community-based autopsy cohort (N = 420), we ascertained opioid and nonsteroidal anti-inflammatory drug (NSAID) use over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDDs)...
April 25, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28448946/oral-administration-of-methysticin-improves-cognitive-deficits-in-a-mouse-model-of-alzheimer-s-disease
#7
Athanassios Fragoulis, Stephanie Siegl, Markus Fendt, Sandra Jansen, Ulf Soppa, Lars-Ove Brandenburg, Thomas Pufe, Joachim Weis, Christoph Jan Wruck
INTRODUCTION: There is increasing evidence for the involvement of chronic inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD). Nuclear factor erythroid 2-related factor 2 (Nrf2) is an anti-inflammatory transcription factor that regulates the oxidative stress defense. Our previous experiments demonstrated that kavalactones protect neuronal cells against Amyloid β (Aβ)-induced oxidative stress in vitro by Nrf2 pathway activation. Here, we tested an in vivo kavalactone treatment in a mouse model of AD...
April 19, 2017: Redox Biology
https://www.readbyqxmd.com/read/28448871/immunomodulatory-effects-of-stem-cells-therapeutic-option-for-neurodegenerative-disorders
#8
REVIEW
Martin Caprnda, Peter Kubatka, Katarina Gazdikova, Iveta Gasparova, Vanda Valentova, Nadezda Stollarova, Giampiero La Rocca, Nazarii Kobyliak, Jozef Dragasek, Ioana Mozos, Robert Prosecky, Dario Siniscalco, Dietrich Büsselberg, Luis Rodrigo, Peter Kruzliak
Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448247/oleuropein-isolated-from-fraxinus-rhynchophylla-inhibits-glutamate-induced-neuronal-cell-death-by-attenuating-mitochondrial-dysfunction
#9
Mi Hye Kim, Ju-Sik Min, Joon Yeop Lee, Unbin Chae, Eun-Ju Yang, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Glutamate-induced neurotoxicity is related to excessive oxidative stress accumulation and results in the increase of neuronal cell death. In addition, glutamate has been reported to lead to neurodegenerative diseases, including Parkinson's and Alzheimer's diseases.It is well known that Fraxinus rhynchophylla contains a significant level of oleuropein (Ole), which exerts various pharmacological effects. However, the mechanism of neuroprotective effects of Ole is still poorly defined. In this study, we aimed to investigate whether Ole prevents glutamate-induced toxicity in HT-22 hippocampal neuronal cells...
April 27, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28447730/pioglitazone-ameliorates-a%C3%AE-42-deposition-in-rats-with-diet-induced-insulin-resistance-associated-with-akt-gsk3%C3%AE-activation
#10
Sisi Yang, Zhe Chen, Ming Cao, Renjie Li, Zhigang Wang, Muxun Zhang
Pioglitazone may have potential benefits as an alternative therapeutic treatment for patients with Alzheimer's disease (AD), particularly in individuals that also have comorbid diabetes; however, the mechanisms of action remain unclear. The present study aimed to explore the effects of pioglitazone on amyloid β, isoform 42 (Aβ42) deposition in rats with diet‑induced insulin resistance (IR). Diet‑induced IR model rats were established in the presence or absence of pioglitazone. Plasma glucose and insulin levels, and cerebrospinal fluid insulin levels were measured; in addition, hippocampal tissues were collected for immunohistochemical analysis of Aβ42 expression...
March 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#11
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28446944/protective-effects-of-proline-rich-peptide-in-a-rat-model-of-alzheimer-disease-an-electrophysiological-study
#12
Naser Khalaji, John Sarkissian, Vergine Chavushyan, Vaghinak Sarkisian
INTRODUCTION: Alzheimer disease (AD) is the most common form of dementia in the elderly that slowly destroys memory and cognitive functions. The disease has no cure and leads to significant structural and functional brain abnormalities. To facilitate the treatment of this disease, we aimed to investigate proline-rich peptide (PRP-1) action of hypothalamus on hippocampal (HP) neurons and dynamics of their recovery, after intracerebroventricular (ICV) injection of amyloid-β (Aβ). METHODS: Experiments were carried out on 24 adult, male Albino rats (average weight: 230±30 g)...
January 2017: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#13
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28446207/memory-is-preserved-in-older-adults-taking-at1-receptor-blockers
#14
Jean K Ho, Daniel A Nation
BACKGROUND: Prior work suggests that some but not all antihypertensive treatments may benefit cognition and risk for Alzheimer's disease, independent of stroke. Angiotensin II receptor blockers (ARBs) have been highlighted as one antihypertensive drug class that may confer greatest benefit. METHODS: The participants comprised 1626 nondemented adults, aged 55-91 years, recruited from Alzheimer's Disease Neuroimaging Initiative sites. Three groups were compared: ARB users (HTN-ARBs), other antihypertensive drug users (HTN-Other), and normotensives...
April 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28445082/the-impact-of-%C3%AE-amyloid-positron-emission-tomography-on-the-diagnostic-and-treatment-decisions-of-dementia-experts
#15
Michael L Ganz, Alie F Tawah, Shien Guo, Abhishek S Chitnis, Hedwig Silies, Barbara Schäuble, Aleksandar Jovalekic, Norman L Foster
AIM: Amyloid positron emission tomography (aPET) measurement of Alzheimer's disease (AD) pathology could improve the accurate diagnosis of cognitive disorders. Appropriate use criteria recommend that only dementia experts order aPET. MATERIALS & METHODS: We surveyed 145 dementia experts about their current approaches to evaluation and treatment and the likely influence of aPET. RESULTS: Experts expected aPET to alter diagnostic procedures and patient management and also increase diagnostic certainty...
April 26, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28442677/1-2-3-triazolyl-esterization-of-pak1-blocking-propolis-ingredients-artepillin-c-arc-and-caffeic-acid-ca-for-boosting-their-anti-cancer-anti-pak1-activities-along-with-cell-permeability
#16
Hideaki Takahashi, Binh Cao Quan Nguyen, Yoshihiro Uto, Md Shahinozzaman, Shinkichi Tawata, Hiroshi Maruta
Artepillin C (ARC) and caffeic acid (CA) are among the major anti-cancer ingredients of propolis, and block the oncogenic/melanogenic/ageing kinase PAK1. However, mainly due to their COOH moiety, cell-permeability of these herbal compounds is rather limited. Thus, in this study, in an attempt to increase their cell-permeability without any significant loss of their water-solubility, we have esterized both ARC and CA with the water-soluble 1,2,3-triazolyl alcohol through Click Chemistry. We found that this esterization boosts the anti-cancer activity of ARC and CA by 100 and over 400 folds, respectively, against the PAK-dependent growth of A549 lung cells, but show no effect on the PAK1-independent growth of B16F10 melanoma cells...
April 24, 2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28442538/peripheral-tumor-necrosis-factor-alpha-tnf-%C3%AE-modulates-amyloid-pathology-by-regulating-blood-derived-immune-cells-and-glial-response-in-the-brain-of-ad-tnf-transgenic-mice
#17
Evi Paouri, Ourania Tzara, Georgia-Ioanna Kartalou, Sofia Zenelak, Spiros Georgopoulos
Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the central nervous system can provide potential therapeutic targets. TNF-α is a pro-inflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear...
April 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28442406/anti-amnesic-effect-of-extract-and-alkaloid-fraction-from-aerial-parts-of-peganum-harmala-on-scopolamine-induced-memory-deficits-in-mice
#18
Wei Liu, Yudan Zhu, Yongli Wang, Shenglan Qi, Yuwen Wang, Chao Ma, Shuping Li, Bo Jiang, Xuemei Cheng, Zhengtao Wang, Zhenyu Xuan, Changhong Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches...
April 22, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28442357/dl-3-n-butylphthalide-promotes-neuroplasticity-and-motor-recovery-in-stroke-rats
#19
Yefei Sun, Xi Cheng, Huibin Wang, Xiaopeng Mu, Yifan Liang, YuJia Luo, Huiling Qu, Chuansheng Zhao
BACKGROUNDS AND AIMS: Racemic l-3-n-butylphthalide (dl-NBP), is able to achieve a functional recovery in animal models of cerebral ischemia, vascular dementia, and Alzheimer's disease. In this study, we investigated the effect of dl-NBP on axonal growth, neurogenesis and behavioral performances in rats with cerebral ischemia. METHODS: Focal cerebral ischemia in rats was produced by intracerebral injection of endothelin-1. Starting from postoperative day 7, the experimental rats were administered 70mg/kg dl-NBP by oral gavage for two weeks...
April 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28442348/upregulation-of-neurotrophins-by-s-47445-a-novel-positive-allosteric-modulator-of-ampa-receptors-in-aged-rats
#20
Francesca Calabrese, Elisa Savino, Elisabeth Mocaer, Sylvie Bretin, Giorgio Racagni, Marco A Riva
At molecular levels, it has been shown that aging is associated with alterations in neuroplastic mechanisms. In this study, it was examined if the altered expression of neurotrophins observed in aged rats could be corrected by a chronic treatment with S 47445 (1-3-10mg/kg, p.o.), a novel selective positive allosteric modulator of the AMPA receptors. Both the mRNA and the protein levels of the neurotrophins Bdnf, NT-3 and Ngf were specifically measured in the prefrontal cortex and hippocampus (ventral and dorsal) of aged rats...
April 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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