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Alzheimer's disease

Li Cheng, Jun Zhang, Xin-Yi Li, Li Yuan, Yan-Fang Pan, Xiao-Rong Chen, Tian-Ming Gao, Jian-Tian Qiao, Jin-Shun Qi
Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid β protein, and investigated the neuroprotection of the anti-Aβ31-35 antibody against Aβ1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats...
October 26, 2016: Hippocampus
Begüm Nurpelin Sağlık, Sinem Ilgın, Yusuf Özkay
Donepezil (DNP), an acetylcholinesterase (AChE) inhibitor, is one of the most preferred choices in Alzheimer diseases (AD) therapy. In the present study, 38 new DNP analogues were synthesized. Structures of the synthesized compounds (1-38) were elucidated by IR, (1)H NMR, (13)C NMR and HRMS spectroscopic methods and elemental analysis. Inhibitory potential of the compounds on cholinesterase enzymes was investigated. None of the compounds displayed significant activity on butyrylcholinesterase (BChE) enzyme...
October 19, 2016: European Journal of Medicinal Chemistry
Karla A Mark, Kathleen J Dumas, Dipa Bhaumik, Birgit Schilling, Sonnet Davis, Tal Ronnen Oron, Dylan J Sorensen, Mark Lucanic, Rachel B Brem, Simon Melov, Arvind Ramanathan, Bradford W Gibson, Gordon J Lithgow
Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer's disease, Parkinson's disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1...
October 25, 2016: Cell Reports
Xin Tan, Peng Fang, Jie An, Huan Lin, Yi Liang, Wen Shen, Xi Leng, Chi Zhang, Yanting Zheng, Shijun Qiu
INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) have usually been found cognitive impairment associated with brain white matter (WM) abnormalities. However, findings have varied across studies, and any potential relationship with Alzheimer's disease (AD) remains unclear. The aim of this study was to assess the whole-brain WM integrity of T2DM patients and to compare our findings with those of published AD cases. METHODS: In this study, we used diffusion tensor imaging (DTI) combined with tract-based spatial statistics (TBSS) to investigate whole-brain WM abnormalities in 48 T2DM patients and 48 healthy controls...
October 25, 2016: Neuroradiology
Ruchi Malik, Bhanwar Singh Choudhary, Shubham Srivastava, Pakhuri Mehta, Manish Sharma
Alzheimer's disease (AD), a progressive neurodegenerative disorder is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine via inhibiting acetylcholinesterase (AChE). The present study involves identification of newer AChE inhibitors by dual approach of e-pharmacophore and structure based virtual screening of Asinex library. Robustness of docking protocol was validated by enrichment calculation with ROC value 0...
October 26, 2016: Journal of Biomolecular Structure & Dynamics
Daniel Vaiman, Francisco Miralles
Preeclampsia is a major pregnancy disease, explained partly by genetic predispositions. STOX1, a transcription factor discovered in 2005, was the first gene directly associated with genetic forms of the disease. Alterations of STOX1 expression as well as STOX1 variants have also been associated to Alzheimer's disease. These observations make of this gene a putative therapeutic target. Area covered: Two major isoforms (STOX1A and STOX1B) are encoded by the gene and are theoretically able to compete for the same binding site, while only the most complete (STOX1A) is supposed to be able to activate gene expression...
October 26, 2016: Expert Opinion on Therapeutic Targets
Size Zheng, Leili Javidpour, Katherine S Shing, Muhammad Sahimi
It is well understood that in some cases proteins do not fold correctly and, depending on their environment, even properly-folded proteins change their conformation spontaneously, taking on a misfolded state that leads to protein aggregation and formation of large aggregates. An important factor that contributes to the aggregation is the interactions between the misfolded proteins. Depending on the aggregation environment, the aggregates may take on various shapes forming larger structures, such as protein plaques that are often toxic...
October 7, 2016: Journal of Chemical Physics
A Del Sole, S Malaspina, Alberto Magenta Biasina
Neuroimaging, both with magnetic resonance imaging (MRI) and positron emission tomography (PET), has gained a pivotal role in the diagnosis of primary neurodegenerative diseases. These two techniques are used as biomarkers of both pathology and progression of Alzheimer's disease (AD) and to differentiate AD from other neurodegenerative diseases. MRI is able to identify structural changes including patterns of atrophy characterizing neurodegenerative diseases, and to distinguish these from other causes of cognitive impairment, e...
October 26, 2016: Functional Neurology
Bharat Bhusan Subudhi, Pratap Kumar Sahu
Oxidative stress in brain underlies the major neurological disorders including Alzheimer's disease (AD) and Parkinson's disease (PD). Peripherally, Angiotensin-II is a major effector of inflammation. Identification of its capacity to access brain during hypertension, as well as location of central rennin angiotensin system have led to its recognition as the major effector of oxidative stress in brain. Clinical uses of antioxidants to antagonize this oxidative stress have mostly failed. In this scenario, AT1 blockers have been investigated to prevent neurodegeneration...
October 24, 2016: Mini Reviews in Medicinal Chemistry
Jan Bressler, Thomas H Mosley, Alan Penman, Rebecca F Gottesman, Beverly Gwen Windham, David S Knopman, Lisa M Wruck, Eric Boerwinkle
Alzheimer's disease (AD) is the most common form of dementia and is characterized by impairment in memory, behavioral changes, and gradual loss of autonomy. Since there is a long latent period prior to diagnosis, the aim of this study was to determine whether twenty single nucleotide polymorphisms identified in genome-wide association analyses of AD are associated with cognitive change in 8,320 white and 2,039 African-American middle-aged adults enrolled in the prospective Atherosclerosis Risk in Communities (ARIC) study...
October 26, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Erik C B Johnson, Jing Kang
A small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzheimer's disease in which memory deficits are a hallmark feature. We did not observe a significant rescue effect with ISRIB treatment on spatial learning and memory as assessed in the Morris water maze in J20 mice...
2016: PeerJ
Kei Sasaki, Norihide Maikusa, Etsuko Imabayashi, Tetsuya Yuasa, Hiroshi Matsuda
INTRODUCTION: Amyloid positron-emission tomography (PET) imaging with (11)C-Pittsburgh compound B (PiB) is an effective tool for assessing brain amyloid deposits. PET imaging, however, can suffer from the partial volume effect (PVE). PVE has been corrected using MRI (magnetic resonance imaging) image data. However, correction of the PVE of PET using MRI usually requires two separate procedures, imposing a burden on patients and leading to low throughput and inefficient diagnoses. The advent of PET/computed tomography (PET/CT) may potentially overcome these problems and offer higher throughput and reliable quantification of amyloid plaques and assessment of Alzheimer disease (AD)...
October 2016: Brain and Behavior
Lakshini H S Mendis, Angus C Grey, Richard L M Faull, Maurice A Curtis
INTRODUCTION: Alzheimer's disease (AD), the leading cause of dementia, is pathologically characterized by β-amyloid plaques and tau tangles. However, there is also evidence of lipid dyshomeostasis-mediated AD pathology. Given the structural diversity of lipids, mass spectrometry is a useful tool for studying lipid changes in AD. Although there have been a few studies investigating lipid changes in the human hippocampus in particular, there are few reports on how lipids change in each hippocampal subfield (e...
October 2016: Brain and Behavior
Md Sahab Uddin, Abdullah Al Mamun, Md Sarwar Hossain, Farjana Akter, Mohammed Ashraful Iqbal, Md Asaduzzaman
Neurodegenerative diseases are incurable and debilitating conditions that result in the progressive degeneration of nerve cells, which affect the cognitive activity. Currently, as a result of multiple studies linking Alzheimer's disease (AD) to oxidative damage, the uses of natural antioxidant to prevent, delay, or enhance the pathological changes underlying the progression of AD has received considerable attention. Therefore, this study was aimed at examining the effect of ethanolic extracts of Phyllanthus emblica (EEPE) ripe (EEPEr) and EEPE unripe (EEPEu) fruits on cognitive functions, brain antioxidant enzymes, and acetylcholinesterase (AChE) activity in rat...
October 2016: Annals of Neurosciences
Xianjuan Kou, Xingran Liu, Xianbing Chen, Jie Li, Xiaoqi Yang, Jingjing Fan, Yi Yang, Ning Chen
The underlying molecular mechanisms for aging-related neurodegenerative diseases such as Alzheimer's disease (AD) are not fully understood. Currently, growing evidences have revealed that microRNAs (miRNAs) are involved in aging and aging-related diseases. The up-regulation of miR-34a has been reported to be associated with aging-related diseases, and thus it should be a promising therapeutic target. Ampelopsin, also called dihydromyricetin (DHM), a natural flavonoid from Chinese herb Ampelopsis grossedentata, has been reported to possess multiple pharmacological functions including anti-inflammatory, anti-oxidative and anti-cancer functions...
October 21, 2016: Oncotarget
Nicholas Zareifopoulos, Costas Papatheodoropoulos
The 5-HT7R is the most recently cloned serotonin receptor and thus one the least studied. Many drugs, experimental and in clinical use bind to 5-HT7 with high affinity, though their effects have yet to be clearly elucidated. Its physiological function, though not completely clear, is mostly associated with learning and memory, with both agonists and antagonists possessing subtle procognitive and promnesic properties. We consider it a promising area of research, though still in its infancy, which may one day lead to clinical benefits for patients with various afflictions characterised by cognitive dysfunction, particularily autism spectrum disorder, fragile X syndrome and Alzheimer's disease...
October 22, 2016: Neurobiology of Learning and Memory
Gulben Senturk, Basar Bilgic, Ali Bilgin Arslan, Ali Bayram, Hasmet Hanagasi, Hakan Gurvit, Murat Emre
BACKGROUND: Anosognosia is a common feature in Alzheimer's disease (AD). The brain substrates of anosognosia are not fully understood, and less is known about the cognitive substrates of anosognosia in prodromal and early stages of AD. METHODS: Fourty-seven patients with amnestic-type mild cognitive impairment (aMCI) (n = 26) and early-stage AD (n = 21) were included, and Clinical Insight Rating Scale and Anosognosia Questionnaire for Dementia (AQ-D) were used to assess anosognosia...
October 26, 2016: International Psychogeriatrics
Sun Kyung Kim, Myonghwa Park, Yunhwan Lee, Seong Hye Choi, So Young Moon, Sang Won Seo, Kyung Won Park, Bon D Ku, Hyun Jeong Han, Kee Hyung Park, Seol-Heui Han, Eun-Joo Kim, Jae-Hong Lee, Sun A Park, Yong S Shim, Jong Hun Kim, Chang Hyung Hong, Duk L Na, Byoung Seok Ye, Hee Jin Kim, Yeonsil Moon
BACKGROUND: Personality may predispose family caregivers to experience caregiving differently in similar situations and influence the outcomes of caregiving. A limited body of research has examined the role of some personality traits for health-related quality of life (HRQoL) among family caregivers of persons with dementia (PWD) in relation to burden and depression. METHODS: Data from a large clinic-based national study in South Korea, the Caregivers of Alzheimer's Disease Research (CARE), were analyzed (N = 476)...
October 26, 2016: International Psychogeriatrics
Enrica Cavedo, Bruno Dubois, Olivier Colliot, Simone Lista, Bernard Croisile, Guy Louis Tisserand, Jacques Touchon, Alain Bonafe, Pierre J Ousset, Olivier Rouaud, Fréderic Ricolfi, Alain Vighetto, Florence Pasquier, Samantha Galluzzi, Christine Delmaire, Mathieu Ceccaldi, Nadine Girard, Stéphane Lehericy, Françoise Duveau, Marie Chupin, Marie Sarazin, Didier Dormont, Harald Hampel
OBJECTIVE: Cortical thinning, previously identified during prodromal stages of Alzheimer's disease (AD), is a "candidate" biomarker implemented in AD clinical therapy trials. We investigated the effect of donepezil treatment on cortical thickness in mild cognitively impaired subjects with the amnestic syndrome of the hippocampal type, a prodromal at-risk group for progression to AD dementia. METHODS: Data were from a longitudinal analysis of a community-based multicenter suspected prodromal AD cohort diagnosed by the Free and Cued Selective Reminding Test (81 donepezil vs 92 placebo) enrolled in a double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day)...
October 25, 2016: Journal of Clinical Psychiatry
David W Crumpacker
Pseudobulbar affect (PBA) is a socially debilitating condition that primarily affects people with neurologic diseases, such as Alzheimer's disease or multiple sclerosis. This condition is characterized by uncontrolled, exaggerated expressions of laughing or crying-often when the situation does not warrant this behavior. Although the true prevalence of PBA is surprisingly high, this condition remains widely misdiagnosed and underdiagnosed. While its exact etiology is unknown, PBA likely results from disruptions in the brain structures and/or neurotransmitters that regulate emotions...
September 2016: Journal of Clinical Psychiatry
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