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lithium and Alzheimer's

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https://www.readbyqxmd.com/read/29103043/examining-the-relationship-between-trace-lithium-in-drinking-water-and-the-rising-rates-of-age-adjusted-alzheimer-s-disease-mortality-in-texas
#1
Val Andrew Fajardo, Val Andrei Fajardo, Paul J LeBlanc, Rebecca E K MacPherson
BACKGROUND: Alzheimer's disease (AD) mortality rates have steadily increased over time. Lithium, the current gold standard treatment for bipolar disorder, can exert neuroprotective effects against AD. OBJECTIVE: We examined the relationship between trace levels of lithium in drinking water and changes in AD mortality across several Texas counties. METHODS: 6,180 water samples from public wells since 2007 were obtained and averaged for 234 of 254 Texas counties...
October 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29080472/the-expression-of-g-protein-coupled-receptor-kinase-5-and-its-interaction-with-dendritic-marker-microtubule-associated-protein-2-after-status-epilepticus
#2
Xiangchang Zeng, Siyu Chen, Qing Gao, Wenjing Zong, Dejian Jiang, Guirong Zeng, Luping Zhou, Lulu Chen, Wei Luo, Jian Xiao, Bo Xiao, Dongsheng Ouyang, Kai Hu
OBJECTIVE: Acute seizures induced dendritic formation and synaptogenesis promotes aberrant circuitry development and further aggravates underlying conditions towards chronic epilepsy. The G protein-coupled receptor kinase-5 (GRK5) served as a key modulator in neurogenesis and the establishment of functional neuronal circuitry. This included dendritic development, as its dysfunction could cause different central nervous system disorders, including Alzheimer's disease. However, the involvement of GRK5 in the progression of epilepsy remains unclear...
October 13, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28885630/from-direct-to-indirect-lithium-targets-a-comprehensive-review-of-omics-data
#3
REVIEW
Magali Roux, Anthony Dosseto
Metal ions are critical to a wide range of biological processes. Among them, lithium (Li) has been recognised for its benefit as a treatment for bipolar disorder (BD). However, we are yet to grasp the extent of its role in biological processes, despite its molecular targets having been extensively studied. Here we review a wide range of transcriptomic, proteomic and metabolomic studies in order to obtain a full picture of Li effects at various levels. Multifarious patterns of Li-regulated genes, proteins and metabolites are identified...
October 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28880358/-lithium-and-its-protective-effect-in-alzheimer-s-disease
#4
S M Wittenberg, K A Toxopeus, P F J Schulte
Lithium is associated with adverse effects on cognitive functioning. However, there are published trials that have investigated the protective effects of lithium in cognitive decline.<br/> AIM: To review studies that investigate the potentially protective effects of lithium on cognitive disorders.<br/> METHOD: We studied English-language and Dutch reports on controlled, clinical trials published up to October 2016.<br/> RESULTS: We found four relevant articles. Two studies indicated that cognitive functioning remained more stable when patients were given lithium than when they were given a placebo...
2017: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/28832877/association-of-lithium-in-drinking-water-with-the-incidence-of-dementia
#5
Lars Vedel Kessing, Thomas Alexander Gerds, Nikoline Nygård Knudsen, Lisbeth Flindt Jørgensen, Søren Munch Kristiansen, Denitza Voutchkova, Vibeke Ernstsen, Jörg Schullehner, Birgitte Hansen, Per Kragh Andersen, Annette Kjær Ersbøll
Importance: Results from animal and human studies suggest that lithium in therapeutic doses may improve learning and memory and modify the risk of developing dementia. Additional preliminary studies suggest that subtherapeutic levels, including microlevels of lithium, may influence human cognition. Objective: To investigate whether the incidence of dementia in the general population covaries with long-term exposure to microlevels of lithium in drinking water. Design, Setting, and Participants: This Danish nationwide, population-based, nested case-control study examined longitudinal, individual geographic data on municipality of residence and data from drinking water measurements combined with time-specific data from all patients aged 50 to 90 years with a hospital contact with a diagnosis of dementia from January 1, 1970, through December 31, 2013, and 10 age- and sex-matched control individuals from the Danish population...
October 1, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28763060/bace1-inhibition-by-microdose-lithium-formulation-np03-rescues-memory-loss-and-early-stage-amyloid-neuropathology
#6
E N Wilson, S Do Carmo, M F Iulita, H Hall, A Ducatenzeiler, A R Marks, S Allard, D T Jia, J Windheim, A C Cuello
Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology...
August 1, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28753292/synthesis-of-11-c-labeled-rxr-partial-agonist-1-3-5-5-8-8-pentamethyl-5-6-7-8-tetrahydronaphthalen-2-yl-amino-benzotriazole-5-carboxylic-acid-cbt-pmn-by-direct-11-c-carbon-dioxide-fixation-via-organolithiation-of-trialkyltin-precursor-and-pet-imaging-thereof
#7
Osamu Shibahara, Masaki Watanabe, Shoya Yamada, Masaru Akehi, Takanori Sasaki, Akiya Akahoshi, Takahisa Hanada, Hiroyuki Hirano, Shunsuke Nakatani, Hiromi Nishioka, Yasuo Takeuchi, Hiroki Kakuta
The retinoid X receptor (RXR) partial agonist 1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (1; CBt-PMN, Emax = 75%, EC50 = 143 nM) is a candidate for treatment of central nervous system (CNS) diseases such as Alzheimer's and Parkinson's diseases based on reports that RXR-full agonist 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene) shows therapeutic effects on these disease in rodent models. Here, we synthesized carbon-11-labeled ([(11)C]1) as a tracer for positron emission tomography (PET) and used it in a PET imaging study to examine the brain uptake and biodistribution of 1...
August 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28617434/lispro-mitigates-%C3%AE-amyloid-and-associated-pathologies-in-alzheimer-s-mice
#8
Ahsan Habib, Darrell Sawmiller, Song Li, Yang Xiang, David Rongo, Jun Tian, Huayan Hou, Jin Zeng, Adam Smith, Shengnuo Fan, Brian Giunta, Takashi Mori, Glenn Currier, Douglas Ronald Shytle, Jun Tan
Lithium has been marketed in the United States of America since the 1970s as a treatment for bipolar disorder. More recently, studies have shown that lithium can improve cognitive decline associated with Alzheimer's disease (AD). However, the current United States Food and Drug Administration-approved lithium pharmaceutics (carbonate and citrate chemical forms) have a narrow therapeutic window and unstable pharmacokinetics that, without careful monitoring, can cause serious adverse effects. Here, we investigated the safety profile, pharmacokinetics, and therapeutic efficacy of LISPRO (ionic co-crystal of lithium salicylate and l-proline), lithium salicylate, and lithium carbonate (Li2CO3)...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28509380/amyloid-is-essential-but-insufficient-for-alzheimer-causation-addition-of-subcellular-cofactors-is-required-for-dementia
#9
REVIEW
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28436339/cognitive-sequelae-of-lithium-intoxication-a-case-report
#10
Stefan Frisch, Frank Grünwald, Benedikt Friedrichs
Lithium intoxication is known to induce cognitive deficits along with motor and behavioral changes, even in association with normal serum levels. However, cases with comprehensive neuropsychological assessment of the deficits are rare. In our patient, we initially found severe cognitive deficits, including apraxia and visuo-constructive problems, and temporo-parietal FDG-PET hypometabolism. Neuropsychological and imaging findings were highly suggestive of Alzheimer's disease. However, lithium intoxication was suspected to account for these findings because of a Parkinson's syndrome, despite serum levels being in the upper therapeutic range...
April 24, 2017: International Psychogeriatrics
https://www.readbyqxmd.com/read/28423937/concordance-of-several-subcellular-interactions-initiates-alzheimer-s-dementia-their-reversal-requires-combination-treatment
#11
REVIEW
W J Fessel
The pathogenesis of Alzheimer's disease involves multiple pathways that, at the macrolevel, include decreased proliferation plus increased loss affecting neurons, astrocytes, and capillaries and, at the subcellular level, involve several elements: amyloid/amyloid precursor protein, presenilins, the unfolded protein response, the ubiquitin/proteasome system, the Wnt/catenin system, the Notch signaling system, mitochondria, mitophagy, calcium, and tau. Data presented show the intimate, anatomical interactions between neurons, astrocytes, and capillaries; the interactions between the several subcellular factors affecting those cells; and the treatments that are currently available and that might correct dysfunctions in the subcellular factors...
May 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28359852/lithium-and-memantine-improve-spatial-memory-impairment-and-neuroinflammation-induced-by-%C3%AE-amyloid-1-42-oligomers-in-rats
#12
J Budni, D P Feijó, H Batista-Silva, M L Garcez, F Mina, T Belletini-Santos, L R Krasilchik, A P Luz, G L Schiavo, J Quevedo
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The main hallmarks of this disease include progressive cognitive dysfunction and an accumulation of soluble oligomers of β-amyloid (Aβ) 1-42 peptide. In this research, we show the effects of lithium and memantine on spatial memory and neuroinflammation in an Aβ1-42 oligomers-induced animal model of dementia in rats. Aβ 1-42 oligomers were administered intrahippocampally to male wistar rats to induce dementia. Oral treatments with memantine (5mg/kg), lithium (5mg/kg), or both drugs in combination were performed over a period of 17days...
March 27, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28253260/direct-keap1-nrf2-disruption-as-a-potential-therapeutic-target-for-alzheimer-s-disease
#13
Fiona Kerr, Oyinkan Sofola-Adesakin, Dobril K Ivanov, Jemma Gatliff, Beatriz Gomez Perez-Nievas, Hélène C Bertrand, Pedro Martinez, Rebecca Callard, Inge Snoeren, Helena M Cochemé, Jennifer Adcott, Mobina Khericha, Jorge Iván Castillo-Quan, Geoffrey Wells, Wendy Noble, Janet Thornton, Linda Partridge
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding of the mechanisms mediating Nrf2 inhibition in neurodegenerative conditions may therefore direct the design of drugs targeted for the prevention of these diseases with minimal side-effects. Our study provides the first in vivo evidence that specific inhibition of Keap1, a negative regulator of Nrf2, can prevent neuronal toxicity in response to the AD-initiating Aβ42 peptide, in correlation with Nrf2 activation...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28222508/chronic-lithium-treatment-in-a-rat-model-of-basal-forebrain-cholinergic-depletion-effects-on-memory-impairment-and-neurodegeneration
#14
Francesca Gelfo, Debora Cutuli, Annalisa Nobili, Paola De Bartolo, Marcello D'Amelio, Laura Petrosini, Carlo Caltagirone
Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28123400/six-psychotropics-for-pre-symptomatic-early-alzheimer-s-mci-parkinson-s-and-huntington-s-disease-modification
#15
REVIEW
Edward C Lauterbach
The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28093288/assessing-the-impact-of-lithium-chloride-on-the-expression-of-p-glycoprotein-at-the-blood-brain-barrier
#16
Stephanie A Newman, Yijun Pan, Jennifer L Short, Joseph A Nicolazzo
In addition to extruding drugs from the brain, P-glycoprotein (P-gp) at the blood-brain barrier (BBB) facilitates the brain-to-blood clearance of beta-amyloid (Aβ) and is down-regulated in Alzheimer's disease. Studies suggest that the mood-stabilizing drug lithium exerts a protective effect against Alzheimer's disease. Although the mechanisms underlying this effect are not fully understood, evidence suggests that lithium chloride (LiCl) increases P-gp expression in vitro, albeit at concentrations substantially outside the therapeutic window...
January 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#17
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong, Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which is expressed on myeloid cells including microglia in the CNS, has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its transmembrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease; however, how AD risk-conferring variants increase AD risk is not clear. To elucidate the signaling pathways underlying reduced TREM2 expression or loss of function in microglia, we respectively knocked down and knocked out the expression of TREM2 in in vitro and in vivo models...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28002662/association-between-lithium-use-and-risk-of-alzheimer-s-disease
#18
Chin Cheng, Peter Zandi, Elizabeth Stuart, Ching-Heng Lin, Pei-Yu Su, G Caleb Alexander, Tsuo-Hung Lan
OBJECTIVE: Current evidence for the association between use of lithium and risk of dementia is mixed. The objective of this study was to assess the risk of Alzheimer's disease associated with use of lithium. METHODS: A population-based, nested case-control study was conducted using data from the National Health Insurance Research Database in 2002 covering 24.5 million beneficiaries of the Taiwan National Health Insurance Program from January 1, 1997, to December 31, 2009...
February 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27999295/special-issue-molecules-against-alzheimer
#19
EDITORIAL
Michael Decker, Diego Muñoz-Torrero
This Special Issue, entitled "Molecules against Alzheimer", gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27832289/glycogen-synthase-kinase-3%C3%AE-regulates-fractalkine-production-by-altering-its-trafficking-from-golgi-to-plasma-membrane-implications-for-alzheimer-s-disease
#20
Almudena Fuster-Matanzo, Jerónimo Jurado-Arjona, Stefano Benvegnù, Esther García, Patricia Martín-Maestro, Raquel Gómez-Sintes, Félix Hernández, Jesús Ávila
Glycogen synthase kinase-3β (GSK-3β) is a serine-threonine kinase implicated in multiple processes and signaling pathways. Its dysregulation is associated with different pathological conditions including Alzheimer's disease (AD). Here we demonstrate how changes in GSK-3β activity and/or levels regulate the production and subsequent secretion of fractalkine, a chemokine involved in the immune response that has been linked to AD and to other different neurological disorders. Treatment of primary cultured neurons with GSK-3β inhibitors such as lithium and AR-A014418 decreased full-length fractalkine in total cell extracts...
March 2017: Cellular and Molecular Life Sciences: CMLS
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