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Alzheimer's disease

Elise Cornelis, Ellen Gorus, Karen Van Weverbergh, Ingo Beyer, Patricia De Vriendt
BACKGROUND: Several methods have been developed to evaluate activities of daily living (ADLs) in mild cognitive impairment (MCI) and mild dementia. This study evaluated the convergent and concurrent validity between (1) two report-based methods (the advanced (a)- and instrumental (i)-ADL tools) and (2) a performance-based method (the Naturalistic Action Test (NAT)) to check if their ability to differentiate between cognitively healthy comparisons (HCs), persons with MCI, and persons with mild Alzheimer's disease (AD) are comparable to each other...
March 22, 2018: International Psychogeriatrics
Osvaldo P Almeida, Andrew H Ford, Graeme J Hankey, Bu B Yeap, Jonathan Golledge, Leon Flicker
BACKGROUND: Recent research has identified several potentially modifiable risk factors for dementia, including mental disorders. Psychotic disorders, such as schizophrenia and delusional disorder, have also been associated with increased risk of cognitive impairment and dementia, but currently available data difficult to generalise because of bias and confounding. We designed the present study to investigate if the presence of a psychotic disorder increased the risk of incident dementia in later life...
March 22, 2018: Psychological Medicine
Madhusudhanan Gogul Ramnath, Ramaraj Thirugnanasampandan, Nagarajan NagaSundaram, Gunasekaran Bhuvaneswari
BACKGROUND: Genus Isodon (Lamiaceae) is a prolific source for bioactive terpenoids. Nowadays, people move towards natural products because of undesirable effects of chemotherapeutic drugs. OBJECTIVE: In silico and in vitro approach were attempted to screen bioactive terpenoids isolated from Isodon wightii with acetylcholinesterase and histone deacetylase3 receptors, Methods: Terpenoids such as abietic acid, oleanolic acid, α-amyrin acetate, β-amyrin acetate were docked with AchE and HDAC3 receptors using AutoDock Vina (version 1...
March 20, 2018: Current Computer-aided Drug Design
Kyriaki Hatziagapiou, Eleni Kakouri, George I Lambrou, Kostas Bethanis, Petros A Tarantilis
BACKGROUND: Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen nitrogen species, are inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants there is growing interest in Crocus Sativus L...
March 20, 2018: Current Neuropharmacology
Fernanda Silva Ferreira, Helena Biasibetti-Brendler, Paula Pierozan, Felipe Schmitz, Carolina Gessinger Bertó, Caroline Acauan Prezzi, Vanusa Manfredini, Angela T S Wyse
Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites produced in the degradation of tryptophan and have important neurological activities. KYNA/QUIN ratio changes are known to be associated with central nervous system disorders, such Alzheimer, Parkinson, and Huntington diseases. In the present study, we investigate the ability of KYNA in prevent the first events preceding QUIN-induced neurodegeneration in striatal slices of rat. We evaluated the protective effect of KYNA on oxidative status (reactive oxygen species production, antioxidant enzymes activities, lipid peroxidation, nitrite levels, protein and DNA damage, and iNOS immunocontent), mitochondrial function (mitochondrial mass, membrane potential, and respiratory chain enzymes), and Na+ ,K+ -ATPase in striatal slices of rats treated with QUIN...
March 21, 2018: Molecular Neurobiology
Huixin Chen, Siying Xiang, Ling Huang, Jiajia Lin, Shengquan Hu, Shing-Hung Mak, Chuang Wang, Qinwen Wang, Wei Cui, Yifan Han
Tacrine(10)-hupyridone (A10E) was designed as a dual-binding acetylcholinesterase (AChE) inhibitor from the modification of tacrine and a fragment of huperzine A. We have found that A10E effectively inhibited AChE in a mixed competitive manner, with an IC50 of 26.4 nM, which is more potent than those of tacrine and huperzine A. Most importantly, we have shown, for the first time that A10E attenuated scopolamine-induced cognitive impairments without affecting motor function in mice. A10E effectively attenuated impairments of learning and memory to a similar extent as donepezil, an inhibitor of AChE used for treating Alzheimer's disease (AD)...
March 21, 2018: Metabolic Brain Disease
Astrid Eliasen, Kim Peder Dalhoff, Henrik Horwitz
INTRODUCTION: Neurological diseases have a profound impact on quality of life. We investigated the risk of suicide attempt in ten neurological diseases. METHODS: Case-control study. Cases were identified from the Danish Poison Information Centre database in the period 2006-2013. The prevalence of ten neurological diagnoses was compared with the prevalence in a randomly sampled age- and gender-matched control group. RESULTS: We identified 8974 cases of suicidal attempt and 89,740 controls...
March 21, 2018: Journal of Neurology
Perry G Ridge, John S K Kauwe
Purpose of Review: Alzheimer's disease (AD) is the most common form of dementia, affects an increasing number of people worldwide, has a rapidly increasing incidence, and is fatal. In the past several years, significant progress has been made towards solving the genetic architecture of AD, but our understanding remains incomplete and has not led to treatments that either cure or slow disease. There is substantial evidence that mitochondria are involved in AD: mitochondrial functional declines in AD, mitochondrial encoded gene expression changes, mitochondria are morphologically different, and mitochondrial fusion/fission are modified...
2018: Current Genetic Medicine Reports
Reza Karbalaei, Marzieh Allahyari, Mostafa Rezaei-Tavirani, Hamid Asadzadeh-Aghdaei, Mohammad Reza Zali
Aim: Analysis reconstruction networks from two diseases, NAFLD and Alzheimer`s diseases and their relationship based on systems biology methods. Background: NAFLD and Alzheimer`s diseases are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on relation and same spreading pathways of these two diseases. In addition, they have some similar risk factors, exclusively lifestyle such as feeding, exercises and so on...
2018: Gastroenterology and Hepatology From Bed to Bench
T Nimmy John, Subha D Puthankattil, Ramshekhar Menon
Alzheimer's disease (AD), a cognitive disability is analysed using a long range dependence parameter, hurst exponent (HE), calculated based on the time domain analysis of the measured electrical activity of brain. The electroencephalogram (EEG) signals of controls and mild cognitive impairment (MCI)-AD patients are evaluated under normal resting and mental arithmetic conditions. Simultaneous low pass filtering and total variation denoising algorithm is employed for preprocessing. Larger values of HE observed in the right hemisphere of the brain for AD patients indicated a decrease in irregularity of the EEG signal under cognitive task conditions...
April 2018: Cognitive Neurodynamics
Wenjun Fu, Yuan Dai, Tao Ma, Jiangping Wei, Huan Chen, Shijun Xu
Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β (Aβ)-induced neurodegeneration is hypothesized to be the primary pathological mechanism of AD. Tongluo Xingnao effervescent tablets (TXET), based on the traditional Chinese formula Qionggui Tang, have been used to treat AD and other types of dementia in China for decades. In the present study, the effects of TXET on cognition deficit, amyloid-β production, amyloid precursor protein procession and β-secretase expression were investigated in the APPswe/PS1dE9 mouse model of AD...
April 2018: Experimental and Therapeutic Medicine
Lianne Hoeijmakers, Anna Amelianchik, Fleur Verhaag, Janssen Kotah, Paul J Lucassen, A Korosi
Life-time experiences are thought to influence the risk to develop the neurodegenerative disorder Alzheimer's disease (AD). In particular, early-life stress (ES) may modulate the onset and progression of AD. There is recent evidence by our group and others that AD-related neuropathological progression and the associated neuroimmune responses are modulated by ES in the classic APPswe/PS1dE9 mouse model for AD. We here extend our previous study on ES mediated modulation of neuropathology and neuroinflammation and address in the same cohort of mice whether ES accelerates and/or aggravates AD-induced cognitive decline and alterations in the process of adult hippocampal neurogenesis (AHN), a form of brain plasticity...
2018: Frontiers in Aging Neuroscience
Eline T S van Maanen, Tamara S van Steeg, Maurice Ahsman, Maria S Michener, Mary J Savage, Matthew E Kennedy, Huub J Kleijn, Julie A Stone, Meindert Danhof
The abnormal accumulation of amyloid-β (Aβ) in the brain parenchyma has been posited as a central event in the pathophysiology of Alzheimer's disease. Recently, we have proposed a systems pharmacology model of the APP pathway, describing the Aβ precursor protein (APP) metabolite responses (Aβ40, Aβ42, sAPPα and sAPPβ) to β-secretase 1 (BACE1) inhibition (van Maanen et al., 2016). In this investigation this model was challenged to describe Aβ dynamics following γ-secretase (GS) inhibition. This led an extended systems pharmacology model, with separate descriptions to characterize the sequential cleavage steps of APP by BACE1 and GS, to describe the differences in Aβ response to their respective inhibition...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
Jason M Uslaner, Scott D Kuduk, Marion Wittmann, Henry S Lange, Steven V Fox, Chris Min, Natasa Pajkovic, Dawn Harris, Caroline Cilissen, Chantal Mahon, Kate Mostoller, Steve Warrington, Douglas C Beshore
The current standard of care for treating Alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. These drugs improve cognitive function in patients, but also produce unwanted side-effects that limit their efficacy. In an effort to selectively improve cognition and avoid the cholinergic side-effects associated with the standard of care, various efforts have been aimed at developing selective M1 muscarinic receptor activators...
March 21, 2018: Journal of Pharmacology and Experimental Therapeutics
Lawrence Rajendran, Rosa C Paolicelli
Microglia are emerging as key players in neurodegenerative diseases, such as Alzheimer's disease (AD). Thus far, microglia have rather been known as modulator of neurodegeneration with functions limited to neuroinflammation and release of neurotoxic molecules. However, several recent studies have demonstrated a direct role of microglia in "neuro" degeneration observed in AD by promoting phagocytosis of neuronal, in particular, synaptic structures. While some of the studies address the involvement of the β-amyloid peptides in the process, studies also indicate that this could occur independent of amyloid, further elevating the importance of microglia in AD...
March 21, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
William M Vanderheyden, Miranda M Lim, Erik S Musiek, Jason R Gerstner
Sleep-wake abnormalities are common in patients with Alzheimer's disease, and can be a major reason for institutionalization. However, an emerging concept is that these sleep-wake disturbances are part of the causal pathway accelerating the neurodegenerative process. Recently, new findings have provided intriguing evidence for a positive feedback loop between sleep-wake dysfunction and β-amyloid (Aβ) aggregation. Studies in both humans and animal models have shown that extended periods of wakefulness increase Aβ levels and aggregation, and accumulation of Aβ causes fragmentation of sleep...
March 21, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jianjia Fan, Rui Qi Zhao, Cameron Parro, Wenchen Zhao, Hsien-Ya Chou, Jerome Robert, Tarek Z Deeb, Carina Raynoschek, Samantha Barichievy, Ola Engvist, Marcello Maresca, Ryan Hicks, Johan Meuller, Stephen J Moss, Nicholas J Brandon, Michael W Wood, Iva Kulic, Cheryl L Wellington
Apolipoprotein E (apoE) is the primary lipid carrier within the central nervous system (CNS) and the strongest genetic risk factor for late onset Alzheimer's disease (AD). ApoE is primarily lipidated via the ATP-binding cassette transporter 1 (ABCA1), and both are under transcriptional regulation by the liver X nuclear receptor (LXR). Considerable evidence from genetic (using ABCA1 overexpression) and pharmacological (using synthetic LXR agonists) studies in AD mouse models suggests that increased levels of lipidated apoE can improve cognitive performance and, in some strains, can reduce amyloid burden...
March 21, 2018: Journal of Lipid Research
Martine Paquette, Yascara Grisel Luna Saavedra, Judes Poirier, Louise Théroux, Doris Dea, Alexis Baass, Robert Dufour
BACKGROUND: Hypercholesterolemia is a major risk factor for the late-onset form of Alzheimer disease (AD). Loss-of-function (LOF) mutations of PCSK9 and PCSK9 inhibitors lower low-density lipoprotein cholesterol (LDL-C) and have been associated with a reduced risk of cardiovascular disease. The aim of this study was to examine the effect of PCSK9 LOF variants on risk and age of onset of AD. METHODS: A total of 878 participants (410 controls and 468 AD cases) from the Quebec Founder Population were included in the study...
January 1, 2018: Journal of Geriatric Psychiatry and Neurology
Norimichi Shirafuji, Tadanori Hamano, Shu-Hui Yen, Nicholas M Kanaan, Hirotaka Yoshida, Kouji Hayashi, Masamichi Ikawa, Osamu Yamamura, Masaru Kuriyama, Yasunari Nakamoto
Increased plasma homocysteinemia is considered a risk factor of dementia, including Alzheimer's disease (AD) and vascular dementia. However, the reason elevated plasma homocysteinemia increases the risk of dementia remains unknown. A pathological hallmark of AD is neurofibrillary tangles (NFTs) that consist of pathologically phosphorylated tau proteins. The effect of homocysteine (Hcy) on tau aggregation was explored using human neuroblastoma M1C cells that constitutively express human wild-type tau (4R0N) under the control of a tetracycline off system, primary mouse cultured neurons, and by inducing hyperhomocysteinemia in a mouse model of tauopathy (HHCy mice)...
March 17, 2018: International Journal of Molecular Sciences
Ralph N Martins, Victor Villemagne, Hamid R Sohrabi, Pratishtha Chatterjee, Tejal M Shah, Giuseppe Verdile, Paul Fraser, Kevin Taddei, Veer B Gupta, Stephanie R Rainey-Smith, Eugene Hone, Steve Pedrini, Wei Ling Lim, Ian Martins, Shaun Frost, Sunil Gupta, Sid O'Bryant, Alan Rembach, David Ames, Kathryn Ellis, Stephanie J Fuller, Belinda Brown, Samantha L Gardener, Binosha Fernando, Prashant Bharadwaj, Samantha Burnham, Simon M Laws, Anna M Barron, Kathryn Goozee, Eka J Wahjoepramono, Prita R Asih, James D Doecke, Olivier Salvado, Ashley I Bush, Christopher C Rowe, Samuel E Gandy, Colin L Masters
Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques...
2018: Journal of Alzheimer's Disease: JAD
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