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Current Alzheimer Research

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https://www.readbyqxmd.com/read/28093972/conformation-as-the-therapeutic-target-for-neurodegenerative-diseases
#1
Rajaraman Krishnan, Franz Hefti, Haim Tsubery, Michal Lulu, Ming Proschitsky, Richard Fisher
Therapeutic strategies that target pathways of protein misfolding and the toxicity of intermediates along these pathways are mainly at discovery and early development stages, with the exception of monoclonal antibodies that have mainly failed to produce convincing clinical benefits in late stage trials. The clinical failures represent potentially critical lessons for future neurodegenerative disease drug development. More effective drugs may be achieved by pursuing the following two strategies. First, conformational targeting of aggregates of misfolded proteins, rather than less specific binding that includes monomer subunits, which vastly outnumber the toxic targets...
January 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28078981/resilience-to-alzheimer-s-disease-the-role-of-physical-activity
#2
Pedrinolla Anna, Schena Federico, Venturelli Massimo
BACKGROUND: Although Alzheimer's disease (AD) is a neurodegenerative pathology characterized by accumulation of β-amyloid plaques and neurofibrillary tangles at cerebral level, recent studies highlighted that AD might be the result of many altered physiological processes occurring at whole-organism level. The ability to adapt to stressors by "bending" but not "breaking" can be considered as "resilience". Individuals incline to withstand such pathophysiological challenges, can be considered more resilient than those that do not...
January 11, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28017127/marginal-vitamin-a-deficiency-exacerbates-memory-deficits-following-a%C3%AE-1-42-injection-in-rats
#3
Jiaying Zeng, Tingyu Li, Ming Gong, Wei Jiang, Ting Yang, Jie Chen
BACKGROUND: Although clinical vitamin A deficiency (VAD), which is a public health problem throughout the developing world, has been well controlled, marginal vitamin A deficiency (MVAD) is far more prevalent, especially among pregnant women and preschool children in China. Increasing evidence suggests that VAD is involved in the pathogenesis of Alzheimer's disease (AD). However, whether MVAD, beginning early in life, increases the risk of developing AD has yet to be determined. OBJECTIVE: The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats...
December 23, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27978792/predicting-stability-of-mild-cognitive-impairment-mci-findings-of-a-community-based-sample
#4
Sinika Ellendt, Bianca Voß, Nils Kohn, Lisa Wagels, Katharina Goerlich, Eva Drexler, Frank Schneider, Ute Habel
BACKGROUND: Mild Cognitive Impairment (MCI) is a risk factor for Alzheimer's disease (AD) and other forms of dementia. However, much heterogeneity concerning neuropsychological measures, prevalence and progression rates impedes distinct diagnosis and treatment implications. OBJECTIVE: Aim of the present study was the identification of specific tests providing a high certainty for stable MCI and factors that precipitate instability of MCI in a community based sample examined at three measurement points...
December 13, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27978791/exercise-prevents-cognitive-function-decline-and-demyelination-in-the-white-matter-of-app-ps1-transgenic-ad-mice
#5
Lei Zhang, Feng-Lei Chao, Yan-Min Luo, Qian Xiao, Lin Jiang, Chun-Ni Zhou, Yi Zhang, Fu-Lin Lv, Qi He, Jing Ma, Yong Tang
It is unclear whether exercise delays the cognitive function decline and structural changes that occur in Alzheimer's disease (AD). In this study, 6-month-old male APP/PS1 double transgenic mice were exercised by running for 20 min/day for four months, and then the effects of exercise on cognitive function and white matter in these AD mice were investigated. We found that the mean escape latency of the exercised group was significantly decreased compared with that of the sedentary group and that the percentage of time spent in the target quadrant and the target zone frequency were significantly increased...
December 13, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/28000550/the-test-your-memory-tym-test-outperforms-the-mmse-in-the-detection-of-mci-and-dementia
#6
Elizabeth van de Zande, Joseph Cornelis Maria van de Nes, Ingeborg Jansen, Margje Nouelle van den Berg, Anne Floor Zwart, Daniel Bimmel, Gerrit Tjalling Rijkers, Gerda Andringa
The aim of this study was to evaluate the diagnostic accuracy and clinical usability of a Dutch translation of the Test Your Memory (TYM) test in patients with mild cognitive impairment (MCI) and dementia as compared to the Mini-Mental State Examination (MMSE), within the setting of the memory clinic of a general hospital. For this, forty-two participants referred to the memory clinic with memory problems and forty-two healthy controls were assessed using the TYM and the MMSE. We evaluated the sensitivity, specificity and diagnostic accuracy of the TYM and MMSE...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27978793/generation-of-alzheimer-s-disease-transgenic-zebrafish-expressing-human-app-mutation-under-control-of-zebrafish-appb-promotor
#7
Yun-Zhu Pu, Liang Liang, Ai-Ling Fu, Yan Liu, Lan Sun, Qian Li, Dan Wu, Man-Ji Sun, Ying-Ge Zhang, Bao-Quan Zhao
Amyloid peptide precursor (APP) as the precursor protein of peptide beta-amyloid (β-amyloid, Aβ), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD), also has an important effect on the development and progression of AD. Through knocking-in APP gene in animals, numerous transgenic AD models have been set up for the investigation of the mechanisms behind AD pathogenesis and the screening of anti-AD drugs. However, there are some limitations to these models and here is a need for such an AD model that is economic as well as has satisfactory genetic homology with human...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915996/cerebral-microinfarcts-and-dementia-a-systematic-review-and-meta-analysis
#8
Lei Cao, Lan Tan, Hui-Fu Wang, Teng Jiang, Xi-Chen Zhu, Jin-Tai Yu
OBJECTIVE: To systematically review the relationship between the cerebral microinfarcts and dementia. METHODS: We conducted a systematic review and meta-analyses using the MEDLINE, EMBASE,the Cochrane library, and BIOSIS preview for studies published in the period from 1 January 1997 to 1 April 2014. We also searched the reference lists of relevant studies and review articles. Studies had to be controlled, with participants divided into a dementia group and a control group...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#9
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915994/is-educational-attainment-associated-with-increased-risk-of-mortality-in-people-with-dementia-a-population-based-study
#10
Israel Contador, Yaakov Stern, Félix Bermejo-Pareja, Álvaro Sánchez-Ferro, Julián Benito-León
OBJECTIVE: The association between higher education and increased mortality in Alzheimer's disease (AD) is controversial. Further it is unknown whether education predicts survival in all dementia subtypes. We assessed mortality rates and death causes of persons with dementia compared to participants without dementia. METHODS: Participants derive from the Neurological Disorders in Central Spain, a prospective population-based cohort study of older adults. We compared 269 persons with dementia to 2944 participants without dementia...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915993/directed-functional-connectivity-of-posterior-cingulate-cortex-and-whole-brain-in-alzheimer-s-disease-and-mild-cognitive-impairment
#11
Enyan Yu, Zhengluan Liao, Dewang Mao, Qi Zhang, Gongjun Ji, Yumei Li, Zhongxiang Ding
BACKGROUND: Impaired functional connectivity in the default mode network (DMN) is supposedly involved in Alzheimer's disease (AD) progression. The posterior cingulate cortex (PCC) might be an imaging marker for monitoring AD progression. OBJECTIVE: To investigate the alterations in the directed functional connectivity between the PCC and whole brain in patients with AD, patients with mild cognitive impairment (MCI), and healthy controls. METHODS: A total of 116 enrolled participants were divided into three groups: AD (n=32), MCI (n=26), and controls (n=58)...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915992/plasma-phospholipids-are-associated-with-mild-cognitive-impairment-in-type-2-diabetic-patients
#12
Jin-Biao Zhang, Yan-Nan Cong, Zhen-Guang Li, Hai-Rong Sun, Jiang-Shan Zhang, Peng-Fei Wang, Qi-Zhan Wu
Phospholipids (PLs) and their metabolisms are closely allied to nosogenesis and aggravation of Type 2 diabetes mellitus and cognitive impairment. The aim of this study is to characterize the plasma levels of phospholipids in type 2 diabetes patients and type 2 diabetes patients with mild cognitive impairment (MCI), and to identify potential biomarkers of type 2 diabetes patients with MCI. In this cross-sectional study, A total of 374 type 2 diabetes patients were prospectively enrolled. There were 103 patients with MCI and 271 patients without MCI (control)...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27875949/treponema-iron-and-neurodegeneration
#13
A Jolivet-Gougeon, M Bonnaure Mallet
Spirochetes are suspected to be linked to the genesis of neurological diseases, including neurosyphillis or neurodegeneration (ND). Impaired iron homeostasis has been implicated in loss of function in several enzymes requiring iron as a cofactor, formation of toxic oxidative species, inflammation and elevated production of beta-amyloid proteins. This review proposes to discuss the link that may exist between the involvement of Treponema spp. in the genesis or worsening of ND, and iron dyshomeostasis. Proteins secreted by Treponema can act directly on iron metabolism, with hemin binding ability (HbpA and HbpB) and iron reductase able to reduce the central ferric iron of hemin, iron-containing proteins (rubredoxin, neelaredoxin, desulfoferrodoxin metalloproteins, bacterioferritins etc)...
November 21, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27875948/prevalence-incidence-risk-and-protective-factors-of-amnestic-mild-cognitive-impairment-in-the-elderly-in-shanghai
#14
Tao Wang, Shifu Xiao, Kewei Chen, Cece Yang, Shuhui Dong, Yan Cheng, Xia Li, Jinghua Wang, Minjie Zhu, Fuzhong Yang, Guanjun Li, Ning Su, Yuanyuan Liu, Jing Dai, Mingyuan Zhang
Amnestic MCI (aMCI) has notably increased in Shanghai, China. This study was designed to estimate the prevalence and incidence rates of aMCI and to determine the risk and protective factors for aMCI among persons ≥ 60 years-old in Shanghai communities. This 1-year longitudinal study, which surveyed a random sample of 1,302 individuals ≥ 60 years-old, collected baseline data about lifestyle through self-reports, and vascular and comorbid conditions from medical records and a physical examination. We also analyzed a subgroup of individuals ≥ 70 years-old...
November 21, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27842487/molecular-interactions-of-bexarotene-a-retinoid-drug-and-alzheimer-s-a%C3%AE-peptide-a-docking-study
#15
Zeenat Mirza, Mohd Amin Beg
Alzheimer's disease (AD) pathogenesis is primarily hallmarked by the production and accumulation of amyloid beta (Aβ) peptide. Along with the understanding of the neurodegenerative disease progression and its pathophysiological mechanisms, development of anti-Aβ targeted effective therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production, toxicity and removal of Aβ are being attempted worldwide. Prime need is to design inhibitors which can slow down the Aβ aggregation process in a physiological environment...
November 14, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27829339/improved-brain-expression-of-anti-amyloid-%C3%AE-scfv-by-complexation-of-mrna-including-a-secretion-sequence-with-peg-based-block-catiomer
#16
Federico Perche, Satoshi Uchida, Hiroki Akiba, Chin-Yu Lin, Masaru Ikegami, Anjaneyulu Dirisala, Toshihiro Nakashima, Keiji Itaka, Kohei Tsumoto, Kazunori Kataoka
Amyloid β aggregates have been proposed as central effectors in Alzheimer's disease, as evidenced by several passive immunotherapies in clinical trials. We used mRNA encoding anti-amyloid β (Aβ) scFv for passive immunotherapy. These scFvs could recognize amyloid oligomers with significant affinity, delay the aggregation of amyloid β in vitro, and dissociate Aβ aggregates in vitro. Intra-cerebroventricular injection of pDNA and mRNA encoding the scFv resulted in detectable scFv levels in the brain, with higher in vivo expression from mRNA...
November 8, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27829338/electrochemical-biosensor-for-detection-of-glycated-albumin
#17
Edyta Mikuła, Aleksandra Wysłouch-Cieszyńska, Liliya Zhukova, Peter Verwilst, Wim Dehaen, Jerzy Radecki, Hanna Radecka
This paper presents an electrochemical biosensor based on a thiol derivative of a pentetic acid (DPTA) complex with Cu (II) created on a gold electrode surface. His-tagged domains of Receptors for Advanced Glycation End Products (RAGE) have been applied as an analytical active element for the determination of the glycated albumin. DPTA-Cu(II) complex molecules play a double role. They are sites for covalent immobilization of His6- RAGE domains, as well as transducers of the analytical signal. The binding of glycated albumin by His6- RAGE domains causes a variation in the electrochemical properties of the Cu(II) redox centers tethered to the electrode surface...
November 8, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27829337/association-of-rs610932-and-rs670139-polymorphisms-in-the-ms4a-gene-cluster-with-alzheimer-s-disease-an-updated-meta-analysis
#18
Ruixia Zhu, Xu Liu, Zhiyi He
Two large-scale genome-wide association studies have identified rs610932 and rs670139 polymorphisms within the MS4A gene cluster as being significantly associated with susceptibility to Alzheimer's disease (AD) in those with European ancestry. A number of studies have focused on the association between MS4A gene variants and AD in Caucasian and East Asian populations. However, the results remain inconsistent owing to the small sample size in each study and the heterogeneity of the populations, among others...
November 8, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27829336/effectiveness-of-a-standardized-and-specific-follow-up-in-memory-centers-in-patients-with-alzheimer-s-disease
#19
Laure Rouch, Philippe Cestac, Charlène Cool, Catherine Helmer, Jean-François Dartigues, Claudine Berr, Olivier Rouaud, Bruno Vellas, Sandrine Andrieu
OBJECTIVES: To compare the 4-year survival, institutionalization, cognitive and functional decline of Alzheimer's patients with specific follow-up in memory centers versus usual care. DESIGN: Four year longitudinal follow-up. SETTINGS: The French Network of memory centers in Alzheimer's disease (REAL-FR study) and The French population-based study (3C study). PARTICIPANTS: 728 patients aged ≥ 65, living at home, meeting criteria for probable Alzheimer's disease and having Mini Mental State Examination (MMSE) scores between 10 and 26 at baseline were included...
November 8, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27829341/increased-risk-of-dementia-in-patients-with-non-apnea-sleep-disorder
#20
Pi-Shan Sung, Chih-Ching Yeh, Liang-Chao Wang, Peir-Haur Hung, Chih-Hsin Muo, Fung-Chang Sung, Chih-Hung Chen, Kuen-Jer Tsai
BACKGROUND: Sleep disorders other than sleep apnea (non-apnea sleep disorder, NSD), esp. insomnia and excessive daytime sleepiness, has been reported to induce higher risk of cognitive decline and dementia in previous longitudinal follow-up studies. However, large-scale nationwide population-based study may further confirm the association between NSD and dementia. METHODS: It was a nationwide population-based retrospective study. We used data from Taiwan's National Health Insurance Research Database (NHIRD) between January 2000 and December 2011...
November 7, 2016: Current Alzheimer Research
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