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Z L Liao, Y Chen, Y F Tan, J P Zhu, Y J Qiu, S S Lin, M H Wu, Y P Mao, E Y Yu
Objective: To compare the differences of cognitive function, daily living ability and neuropsychiatric symptoms in patients with sporadic type of Alzheimer's disease (AD) under different care modes, and find the most favorable care mode for delaying the progress of disease. Methods: One hundred and twenty cases of AD patients were divided into three groups: Spouse Care Group, Adult Child Care Group and Nursing Home Group. Medical history collection and scale evaluation were carried out by trained specialists on 3 groups of patients and caregivers...
February 19, 2019: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Kenyu Hayashi, Yu Hasegawa, Yushin Takemoto, Cheng Cao, Hiroto Takeya, Yoshihiro Komohara, Akitake Mukasa, Shokei Kim-Mitsuyama
Systemic organ dysfunction is one of the important issues for the patients with Alzheimer's disease (AD) and their caregivers. Recent evidences suggest that periodontitis is a possible risk factor for progression of AD and lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) which is a major periodontopathic bacteria induces cognitive impairment in mice. However, the precise relationships between the brain exposure of Pg-LPS and systemic organ dysfunction in AD patients are still undetermined. In this study, we investigated whether brain exposure of Pg-LPS induced systemic organ dysfunction in a model of AD mouse...
February 17, 2019: Experimental Gerontology
Martial Caillaud, Jérôme Guillard, Damien Richard, Serge Milin, Damien Chassaing, Marc Paccalin, Guylène Page, Agnès Rioux Bilan
As Alzheimer's disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice. We report that trans ε-viniferin could go through the blood brain barrier, reduces size and density of amyloid deposits and decreases reactivity of astrocytes and microglia, after a weekly intraperitoneal injection at 10 mg/kg from 3 to 6 months of age...
2019: PloS One
Md Junaid, Nazrul Islam, Md Kamal Hossain, M Obayed Ullah, Mohammad A Halim
Among neurodegenerative disorders, Alzheimer's disease (AD) is one of the most common disorders showing slow progressive cognitive decline. Targeting acetylcholinesterase (AChE) is one of the major strategies for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are compromised. Herein, we report the design of some copper and other metal based donepezil derivatives, employing density functional theory (DFT). All designed compounds are optimized at the B3LYP/SDD level of theory...
2019: PloS One
Lachlan E McInnes, Asif Noor, Kai Kysenius, Carleen Cullinane, Peter Roselt, Catriona A McLean, Francis C K Chiu, Andrew K Powell, Peter J Crouch, Jonathan M White, Paul S Donnelly
Amyloid-β plaques, consisting of aggregated amyloid-β peptides, are one of the pathological hallmarks of Alzheimer's disease. Copper complexes formed using positron-emitting copper radionuclides that cross the blood-brain barrier and bind to specific molecular targets offer the possibility of noninvasive diagnostic imaging using positron emission tomography. New thiosemicarbazone-pyridylhydrazone based ligands that incorporate pyridyl-benzofuran functional groups designed to bind amyloid-β plaques have been synthesized...
February 20, 2019: Inorganic Chemistry
Song Chen, Su-Ting Chen, Yan Sun, Zheng Xu, Ying Wang, Si-Yuan Yao, Wen-Bing Yao, Xiang-Dong Gao
Our understanding of the mechanisms underlying process in Alzheimer's disease (AD) is far from completion and new therapeutic targets are urgently needed. Recently, the link between dementia and diabetes mellitus (DM) prompted us to search for new therapeutic strategies from glucose metabolism regulators for neurodegeneration. Previous studies have indicated that fibroblast growth factor 21 (FGF21), an attractive and potential therapeutic treatment for DM, may exert diverse effects in the central nervous system...
February 1, 2019: Redox Biology
Mohd Shahnawaz Khan, Md Tabish Rehman, Sheraz Ahmad Bhat, Shams Tabrez, Afzal Hussain, Fohad Mabood Husain, Mohamed F AlAjmi, Salman Freeh Alamery, Sadia Sumbul
Protein aggregation leads to vast conformational changes and plays a key role in the pathogenesis of various neurodegenerative diseases including Alzheimer's and Parkinson's. In the current piece of work, we have explored the interaction of quinoline yellow (QY) with myoglobin (Mb) at two different pH (3.5 and 7.4). Various spectroscopic techniques such as turbidity, Rayleigh light scattering (RLS), UV-Vis absorbance, fluorescence resonance energy transfer (FRET), far UV-CD along with transmission electron microscopy (TEM) and molecular docking have been utilized to characterize dye-induced aggregation in Mb...
February 13, 2019: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Paula Alexandra Postu, Fatima Zahra Sadiki, Mostafa El Idrissi, Oana Cioanca, Adriana Trifan, Monica Hancianu, Lucian Hritcu
The most prevalent neurodegenerative disease is Alzheimer's dementia. It is determined by the deposits of amyloid-beta peptide which leads to memory impairment, oxidative stress, and neurodegeneration. Aromatherapy by using essential oils could represent a natural treatment option for Alzheimer's dementia. Therefore, this study aimed to identify the neuroprotective and nootropic effects of Pinus halepensis essential oil (PNO, 1% and 3%, administered for three weeks) in a rat model of acute amyloid beta (1-42) (Aβ1-42) toxicity...
February 19, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Benjamin L Viglianti, Daniel J Wale, Tianwen Ma, Timothy D Johnson, Nicolaas I Bohnen, Ka Kit Wong, Christy Ky, Kirk A Frey, Danyelle M Townsend, Domenico Rubello, Milton D Gross
PURPOSE: Hyperglycemia affects FDG uptake in the brain, potentially emulating Alzheimer's disease in normal individuals. This study investigates global and regional cerebral FDG uptake as a function of plasma glucose in a cohort of patients. METHODS: 120 consecutive male patients with FDG PET/CT for initial oncologic staging (July-Dec 2015) were reviewed. Patients with dementia, cerebrovascular accident, structural brain lesion, prior oncology treatment or high metabolic tumor burden (recently shown affecting brain FDG uptake) were excluded...
February 20, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
S Benfeito, C Oliveira, C Fernandes, F Cagide, J Teixeira, R Amorim, J Garrido, C Martins, B Sarmento, R Silva, F Remião, E Uriarte, P J Oliveira, F Borges
Alzheimer's disease is an irreversible, complex and progressive neurodegenerative disorder associated with oxidative stress and mitochondrial dysfunction. Exogenous antioxidants can be beneficial for decreasing oxidative stress, as they are able to reward the lack of efficacy of the endogenous defense systems and raise the overall antioxidant response in a pathological condition. Along our overarching project related with the design and development of potent and safe multi-target mitochondriotropic antioxidants, based on dietary antioxidants, novel derivatives were obtained...
February 6, 2019: European Journal of Medicinal Chemistry
Piyoosh Sharma, Avanish Tripathi, Prabhash Nath Tripathi, Santosh Kumar Prajapati, Ankit Seth, Manish Kumar Tripathi, Pavan Srivastava, Vinod Tiwari, Sairam Krishnamurthy, Sushant Kumar Shrivastava
The multitarget-directed strategy offers an effective and promising paradigm to treat the complex neurodegenerative disorder, such as Alzheimer's disease (AD). Herein, a series of N-benzylpiperidine analogs (17-31 and 32-46) were designed and synthesized as multi-functional inhibitors of acetylcholinesterase (AChE) and β-secretase-1 (BACE-1) with moderate to excellent inhibitory activities. Among the tested inhibitors, 25, 26, 40, and 41 presented the most significant and balanced inhibition against both the targets...
February 14, 2019: European Journal of Medicinal Chemistry
Clémence Tomadesso, Julie Gonneaud, Stéphanie Egret, Audrey Perrotin, Alice Pélerin, Robin de Flores, Vincent de la Sayette, Béatrice Desgranges, Gaël Chételat, Renaud La Joie
Amnestic mild cognitive impairment (aMCI) is a clinical entity with various potential etiologies including but not limited to Alzheimer's disease. We examined whether a positive ([18F]Florbetapir) beta amyloid positron emission tomography scan, supporting underlying Alzheimer's disease pathophysiology, was associated with specific memory deficits in 48 patients with aMCI (33 beta amyloid positive, 15 beta amyloid negative). Memory was evaluated using an autobiographical fluency task and a word-list learning task with 2 different encoding types (shallow/incidental versus deep/intentional)...
January 31, 2019: Neurobiology of Aging
Miao Sun, Chengyu Huang, Hui Wang, Huaye Zhang
The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking...
January 30, 2019: Neurobiology of Aging
Zahra Jafari, Megan Okuma, Hadil Karem, Jogender Mehla, Bryan E Kolb, Majid H Mohajerani
Environmental distresses occurring during the sensitive periods of early life may exacerbate the vulnerability to develop physical and mental diseases in old age. Studies have shown the impact of prenatal stress (PS) on the endocrine development and reprogramming of hypothalamic-pituitary-adrenal axis functions in association with cognitive development and susceptibility to neuropsychiatric diseases. Long-term exposure to glucocorticoids can damage the brain and intensify the progression of Alzheimer's disease (AD)-like neuropathological changes, especially in females...
January 30, 2019: Neurobiology of Aging
Nazanin Makkinejad, Julie A Schneider, Junxiao Yu, Sue E Leurgans, Aikaterini Kotrotsou, Arnold M Evia, David A Bennett, Konstantinos Arfanakis
Transactive response DNA-binding protein 43 (TDP-43) pathology is common in old age and is strongly associated with cognitive decline and dementia above and beyond contributions from other neuropathologies. TDP-43 pathology in aging typically originates in the amygdala, a brain region also affected by other age-related neuropathologies such as Alzheimer's pathology. The purpose of this study was two-fold: to determine the independent effects of TDP-43 pathology on the volume, as well as shape, of the amygdala in a community cohort of older adults, and to determine the contribution of amygdala volume to the variance of the rate of cognitive decline after accounting for the contributions of neuropathologies and demographics...
January 31, 2019: Neurobiology of Aging
Zeyang Ji, Hao Li, Zhou Yang, Xian Huang, Xiao Ke, Sehui Ma, Zhijie Lin, Youming Lu, Mingjie Zhang
Kibra is a synaptic scaffold protein regulating learning and memory. Alterations of Kibra-encoding gene WWC1 cause various neuronal disorders, including Alzheimer's disease and Tourette syndrome. However, the molecular mechanism underlying Kibra's function in neurons is poorly understood. Here we discover that Kibra, via its N-terminal WW12 tandem domains, binds to a postsynaptic density enriched protein, Dendrin, with a nanomolar dissociation constant. On the basis of the structure of Kibra WW12 in complex with Dendrin PY motifs, we developed a potent peptide inhibitor capable of specifically blocking the binding between Kibra and Dendrin in neurons...
February 19, 2019: Cell Reports
Yue Leng, Erik S Musiek, Kun Hu, Francesco P Cappuccio, Kristine Yaffe
Dysfunction in 24-h circadian rhythms is a common occurrence in ageing adults; however, circadian rhythm disruptions are more severe in people with age-related neurodegenerative diseases, including Alzheimer's disease and related dementias, and Parkinson's disease. Manifestations of circadian rhythm disruptions differ according to the type and severity of neurodegenerative disease and, for some patients, occur before the onset of typical clinical symptoms of neurodegeneration. Evidence from preliminary studies suggest that circadian rhythm disruptions, in addition to being a symptom of neurodegeneration, might also be a potential risk factor for developing Alzheimer's disease and related dementias, and Parkinson's disease, although large, longitudinal studies are needed to confirm this relationship...
March 2019: Lancet Neurology
Yang Zhang, Junbiao Ying, Jiajun Hong, Fengcheng Li, Tingting Fu, Fengyuan Yang, Guoxun Zheng, Xiaojun Yao, Yan Lou, Yun Qing Qiu, Weiwei Xue, Feng Zhu
Histone deacetylase 6 (HDAC6) plays a key role in a variety of neurological disorders, which makes it attractive drug target for the treatment of Alzheimer's disease, Parkinson disease and memory/learning impairment. The selectivity of HDAC6 inhibitors (sHDAC6Is) are widely considered to be susceptible to their sizes of Cap group and their physicochemical properties of linker or zinc-binding group, which makes the discovery of new sHDAC6Is extremely difficult. With the discovery of the distinct selectivity between Trichostatin A (TSA) enantiomers, the chirality residing in the connective units between TSA's Cap and linker shows a great impact on its selectivity...
February 20, 2019: ACS Chemical Neuroscience
Motohiro Okada, Kouji Fukuyama, Yasuhiro Kawano, Takashi Shiroyama, Yuto Ueda
Deficiencies in N-methyl-d-aspartate (NMDA)/glutamate receptor (NMDAR) signaling have been considered central to the cognitive impairments of schizophrenia; however, an NMDAR antagonist memantine (MEM) improves cognitive impairments of Alzheimer's disease and schizophrenia. These mechanisms of paradoxical clinical effects of NMDAR antagonists remain unclear. To explore the mechanisms by which MK801 and MEM affect thalamocortical transmission, we determined interactions between local administrations of MK801, MEM, system xc- (Sxc), and metabotropic glutamate receptors (mGluRs) on extracellular glutamate and GABA levels in the mediodorsal thalamic nucleus (MDTN) and medial prefrontal cortex (mPFC) using dual-probe microdialysis with ultra-high-pressure liquid chromatography...
February 2019: Pharmacology Research & Perspectives
Giampiero Giovacchini, Elisabetta Giovannini, Elisa Borsò, Patrizia Lazzeri, Mattia Riondato, Rossella Leoncini, Valerio Duce, Andrea Ciarmiello
Neuropathological and clinical evidence indicates that the clinical expression of Alzheimer's disease (AD) occurs as neuropathology exceeds the brain reserve capacity. The brain or cognitive reserve (BCR) hypothesis states that high premorbid intelligence, education, and an active and stimulating lifestyle provide reserve capacity, which acts as a buffer against the cognitive deficits due to accumulating neuropathology. Neuroimaging studies that assessed the BCR hypothesis are critically reviewed with emphasis on study design and statistical analysis...
February 19, 2019: Journal of Cellular Physiology
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