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Current Alzheimer Research

Cornejo-Montes-de-Oca Jose Maria, Hernandez-Soto Rebeca, Isla G Arturo, C E Morado-Urbina, Pena-Ortega Fernando
Amyloid beta inhibits olfactory bulb function. The mechanisms involved in this effect must include alterations in network excitability, inflammation and the activation of different transduction pathways. Thus, here we tested whether tolfenamic acid, a drug that modulates several of these pathological processes, could prevent amyloid beta-induced olfactory bulb dysfunction. • Objective: To test whether tolfenamic acid prevents amyloid beta-induced alterations in olfactory bulb network function, olfaction and GSK3β activity...
February 22, 2018: Current Alzheimer Research
Shohreh Majd, John H T Power
BACKGROUND: Emerging evidence supports the hypothesis that metabolism dysfunction is involved in pathogenesis of Alzheimer's disease (AD). One aspect of metabolic dysfunction includes dysregulation of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) metabolic axis, which is extensively present in some of the leading causes of AD such as cerebrovascular diseases, type 2 diabetes and brain ischaemic events. While the molecular basis underlying this metabolic dysregulation remains a significant challenge, mitochondrial dysfunction due to aging appears to be an essential factor to activate AMPK/mTOR signaling pathway, leading to abnormal neuronal energy metabolism and AD pathology...
February 22, 2018: Current Alzheimer Research
Cedric Annweiler, Lise Doineau, Lucie Gerigne, Anais Provendier, Spyridon N Karras, Olivier Beauchet, Bruno Fantino, Guillaume T Duval
BACKGROUND: Older adults with hypovitaminosis D report more often subjective cognitive complaints, especially with regards to memory. This raises prospects that vitamin D may improve older adults' subjective experience of memory disorders. OBJECTIVE: To determine among older community-dwellers whether higher serum 25-hydroxyvitamin D (25OHD) concentrations were associated with fewer memory complaints, while considering the different subtypes of memory complaints...
February 1, 2018: Current Alzheimer Research
Blanka Klimova, Kamil Kuca, Martin Valis, Jakub Hort
BACKGROUND: Currently, there is a significant increase in the number of older generation groups, which may result in serious economic and social issues. Therefore there is a need to prolong the active life of these older individuals, especially by focusing on modifying lifestyle factors such as healthy nutrition. In fact, recent research has shown that, for example, nuts are an important part of people's healthy diet because they have appeared to be neuroprotective compounds which might maintain or in some cases even improve people's cognitive functions...
February 1, 2018: Current Alzheimer Research
Antonio Martinez-Torteya, Hugo Gomez-Rueda, Victor Trevino, Joshua Farber, Jose Tamez-Pena, For The Alzheimer's Disease Neuroimaging Initiative
BACKGROUND: Diagnosing Alzheimer's disease (AD) in its earliest stages is important for therapeutic and support planning. Similarly, being able to predict who convert from mild cognitive impairment (MCI) to AD would have clinical implications. OBJECTIVES: This study's goals were to identify features from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database associated with the conversion from MCI to AD, and to characterize the temporal evolution of that conversion...
February 1, 2018: Current Alzheimer Research
Richard Cimler, Hana Tomaskova, Jitka Kuhnova, Ondrej Dolezal, Pavel Pscheidl, Kamil Kuca
BACKGROUND: Alzheimer's disease is one of the most common mental illnesses. It is posited that more than 25 % of the population is affected by some mental disease during their lifetime. Treatment of each patient draws resources from the economy concerned. Therefore, it is important to quantify the potential economic impact. METHODS: Agent-based, system dynamics and numerical approaches to dynamic modeling of the population of the European Union and its patients with Alzheimer's disease are presented in this article...
February 1, 2018: Current Alzheimer Research
Kresimir Ukalovic, Sijia Cao, Sieun Lee, Qiaoyue Tang, Mirza Faisal Beg, Marinko V Sarunic, Ging-Yuek R Hsiung, Ian R Mackenzie, Veronica Hirsch-Reinshagen, Jing Z Cui, Joanne A Matsubara
BACKGROUND: Recent work on Alzheimer's disease (AD) diagnosis focuses on neuroimaging modalities; however, these methods are expensive, invasive, and not available to all patients. Ocular imaging of biomarkers, such as drusen in the peripheral retina, could provide an alternative method to diagnose AD. OBJECTIVE: This study compares macular and peripheral drusen load in control and AD eyes. METHOD: Postmortem eye tissues were obtained from donors with a neuropathological diagnosis of AD...
January 23, 2018: Current Alzheimer Research
Giulia Maria Sancesario, Marzia Nuccetelli, Andrea Cerri, Joshua Zegeer, Cinzia Severini, Maria Teresa Ciotti, Massimo Pieri, Alessandro Martorana, Carlo Caltagirone, Robert Nistico, Sergio Bernardini
BACKGROUND: Therapeutic approaches targeting amyloid β-42 (Aβ42) oligomers may represent a promising neuroprotective strategy for the prevention and treatment of Alzheimer's disease (AD). OBJECTIVE: In this study we evaluated the ability of bromelain, a plant cysteine protease derived from pineapple stems, to interact with synthetic Aβ42 monomers and oligomers. We also examined the ability of bromelain to interfere in vitro with synthetic Aβ42 aggregates in the cerebrospinal fluid (CSF) of Alzheimer's disease as well as of control patients affected by other neurological diseases...
January 23, 2018: Current Alzheimer Research
Cassandra Morrison, Sheida Rabipour, Frank Knoefel, Christine Shepard, Vanessa Taler
BACKGROUND: Mild cognitive deficits are more likely to occur with increasing age, and become more pronounced for people diagnosed with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Conventional methods to identify cognitive declines (i.e., neuropsychological testing and clinical judgment) can lead to false positive diagnoses of cognitive impairment. Tools such as electroencephalography (EEG) offer additional measures of cognitive processing, indexing the electrophysiological changes associated with aging, MCI and AD...
January 23, 2018: Current Alzheimer Research
Matthew Davis, Thomas O Connell, Scott Johnson, Stephanie Cline, Elizabeth Merikle, Ferenc Martenyi, Kit N Simpson
Background Alzheimer's disease (AD) can be conceptualized as a continuum: patients progress from normal cognition to mild cognitive impairment (MCI) due to AD, followed by increasing severity of AD dementia. Prior research has measured transition probabilities among later stages of AD, but not for the complete spectrum. Objective To estimate annual progression rates across the AD continuum and evaluate the impact of a delay in MCI due to AD on the trajectory of AD dementia and clinical outcomes. Methods Patient-level longitudinal data from the National Alzheimer's Coordinating Center for n=18,103 patients with multiple visits over the age of 65 were used to estimate annual, age-specific transitional probabilities between normal cognition, MCI due to AD, and AD severity states (defined by Clinical Dementia Rating score)...
January 18, 2018: Current Alzheimer Research
Cecilia Camarda, Carmela Pipia, Delia Azzarello, Iacopo Battaglini, Giovanni Romeo, Marcello Chiodi, Rosolino Camarda
BACKGROUND: Mild Cognitive Impairment (MCI) is a transitional state between normal cognition and dementia. OBJECTIVE: The aim of this study is to investigate the role of vascular risk factors, vascular diseases, cerebrovascular disease and brain atrophy in a large hospital-based cohort of MCI types including 471 amnestic MCI (a-MCI), 693 amnestic MCI multiple domain (a-MCImd), 322 single non-memory MCI (snm-MCI), and 202 non amnestic MCI multiple domain (na-MCImd)...
January 18, 2018: Current Alzheimer Research
Huifeng Zhang, Dan Liu, Huanhuan Huang, Yujia Zhao, Hui Zhou
BACKGROUND: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. METHODS: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis...
January 18, 2018: Current Alzheimer Research
Antonella Alberici, Viviana Cristillo, Stefano Gazzina, Alberto Benussi, Alessandro Padovani, Barbara Borroni
Frontotemporal Dementia (FTD) is a neurodegenerative disorder which asymmetrically affects the frontotemporal lobes; it is characterized by behavioural abnormalities, language impairment, and deficits of executive functions. Behavioural variant FTD (bvFTD) and Primary Progressive Aphasias (PPAs) represent the most common phenotypes. The identification of mutations responsible for autosomal dominant inherited disorder, namely Microtubule Associated Protein Tau (MAPT), Granulin (GRN) and chromosome 9 open reading frame 72 (C9orf72) mutations, contributed to elucidate the molecular pathways involved in brain depositions of either Tau or TAR DNA-binding protein 43 (TDP43) inclusions...
January 18, 2018: Current Alzheimer Research
J K Chang, A Leso, G M Subaiea, A Lahouel, A Masoud, F Mushtaq, R Deeb, A Eid, M Dash, S W Bihaqi, N H Zawia
OBJECTIVE: Tangles are deposits of hyperphosphorylated tau, which are found in multiple neurodegenerative disorders that are referred to as tauopathies, of which Alzheimer's disease (AD) is the most common. Tauopathies are clinically characterized by dementia and share in common cortical lesions composed of aggregates of the protein tau. METHODS: In this study, we explored the therapeutic potential of tolfenamic acid (TA), in modifying disease processes in a transgenic animal model that carries the human tau gene (hTau)...
January 18, 2018: Current Alzheimer Research
Naima Chalour, Agathe Maoui, Patrice Rat, France Massicot, Melody Dutot, Anne-Marie Faussat, Estelle Devevre, Astrid Limb, Jean-Michel Warnet, Jacques Treton, Virginie Dinet, Frederic Mascarelli
BACKGROUND: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2-nonenal (HNE). AMD has been named the AD in the eye. The Müller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status. Any MC dysfunction results in retinal neurodegeneration. OBJECTIVES: We investigated the effects of HNE in human MC...
January 18, 2018: Current Alzheimer Research
Raul Romero Sevilla, Ignacio Casado Naranjo, Juan Carlos Portilla Cuenca, Beatriz Duque de San Juan, Jose Manuel Fuentes Rodriguez, Fidel Lopez Espuela
BACKGROUND: Evidence of the effect of vascular risk factors and white matter lesions on progression of mild cognitive impairment (MCI) to dementia is not conclusive. OBJECTIVE: To analyze the impact of these factors on MCI progression to dementia from a global perspective. METHODS: Our study included a population of 105 patients with MCI. RESULTS: After a mean follow-up period of 3.09 years (range, 2-3.79), 47 patients (44...
January 18, 2018: Current Alzheimer Research
Robert E Becker, Nigel H Greig, Debomoy K Lahiri, Joseph Bledsoe, Sarah Majercik, Clive Ballard, Dag Aarsland, Lon S Schneider, Douglas Flanagan, Ramprakash Govindarajan, Mary Sano, Luigi Ferrucci, Dimitrios Kapogiannis
BACKGROUND: Concussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities. Multiple clinical trials targeting mechanisms based on the Amyloid Hypothesis of AD have so far failed, indicating that it is prudent for new drug developments to also pursue mechanisms independent of the Amyloid Hypothesis. To address these issue, we have proposed the use of an animal model of concussion/TBI as a supplement to AD transgenic mice to provide an indication of an AD drug candidate's potential for preventing PPCD and resulting progression towards dementia in AD...
January 10, 2018: Current Alzheimer Research
Hui Liu, Golam T Saffi, Maryam S Vasefi, Youngjik Choi, Jeff S Kruk, Nawaz Ahmed, Nyasha Gondora, John Mielke, Zoya Leonenko, Michael A Beazely
PDGFβ receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins. METHODS: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD). In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid- treatment for 24 h decreased surviving cell number in a concentration-dependent manner...
January 9, 2018: Current Alzheimer Research
Olivier Vercruysse, Claire Paquet, Audrey Gabelle, Xavier Delbeuck, Frederic Blanc, David Wallon, Julien Dumurgier, Eloi Magnin, Olivier Martinaud, Barbara Jung, Olivier Bousiges, Sylvain Lehmann, Constance Delaby, Muriel Quillard-Murain, Katell Peoc'h, Jean-Louis Laplanche, Elodie Bouaziz-Amar, Didier Hannequin, Bernard Sablonniere, Luc Buee, Jacques Hugon, Susanna Schraen, Florence Pasquier, Stephanie Bombois
BACKGROUND: Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD). OBJECTIVE: The aim of this study was to test the hypothesis of misdiagnoses for these patients. METHOD: Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF A1-42, T-tau and P-tau biomarkers and clinical follow-up, were included...
January 9, 2018: Current Alzheimer Research
Wenwen Bai, Tiaotiao Liu, Mengmeng Dou, Mi Xia, Jun Lu, Xin Tian
INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative disease that gradually induces cognitive deficits in the elderly and working memory impairment is typically observed in AD. Amyloid-β peptide (Aβ) is a causative factor for the cognitive impairments in AD. Gamma oscillations have been recognized to play important roles in various cognitive functions including working memory. Previous study reported that Aβ induces gamma oscillation dysfunction in working memory. Repetitive transcranial magnetic stimulation (rTMS) represents a technique for noninvasive stimulation to induce cortical activity and excitability changes and has been accepted for increasing brain excitability and regulating cognitive behavior...
January 9, 2018: Current Alzheimer Research
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