International Journal of Alzheimer's Disease最新文献

{"title":"Cumulative effect of depression on dementia risk.","authors":"J Olazarán,&nbsp;R Trincado,&nbsp;F Bermejo-Pareja","doi":"10.1155/2013/457175","DOIUrl":"https://doi.org/10.1155/2013/457175","url":null,"abstract":"<p><p>Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD), past depression (pD), present depression (prD), and present and past depression (prpD). Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women), and 1,376 (81.6%) subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01-3.35] for prD and 2.73 [1.08-6.87] for prpD), and on dementia due to AD (OR 1.98 [0.98-3.99] for prD and OR 3.98 [1.48-10.71] for prpD) (fully adjusted models, nD as reference). Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":" ","pages":"457175"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/457175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40265990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studies on interaction of buffalo brain cystatin with donepezil: an Alzheimer's drug.","authors":"Fakhra Amin, Bilqees Bano","doi":"10.1155/2013/842689","DOIUrl":"10.1155/2013/842689","url":null,"abstract":"<p><p>When drugs bind to a protein, the intramolecular structures can be altered, resulting in conformational change of the protein. Donepezil, an Acetyl Cholinesterase inhibitor (AChE), is commonly prescribed to patients with Alzheimer's disease (AD) to enhance cholinergic neurotransmission. It is the \"first-line\" agents in the treatment of Alzheimer's disease used to improve cognitive function in the disease. In the present study, a cysteine protease inhibitor (cystatin) has been isolated from buffalo brain using alkaline treatment, 40 to 60% ammonium sulphate fractionation and gel filtration chromatography on Sephadex G-75 with % yield of 64.13 and fold purification of 384.7. The purified inhibitor (Buffalo Brain Cystatin, (BBC)) was eluted as a single papain inhibitory peak which migrated as single band on native PAGE; however, on SDS-PAGE with and without beta mercaptoethanol ( β ME) BBC gave two bands of M W 31.6 and 12.4 KDa, respectively. The molecular weight determined by gel filtration came out to be 43.6 KDa. The UV spectra of cystatin on interaction with donepezil suggested a conformational change in the protein. The fluorescence spectra of BC-donepezil composite show structural changes indicating 40 nm red shift with significant increase in fluorescence intensity of cystatin in the presence of donepezil representing an unfolding of cystatin on interaction, which is an indication of side effect of donepezil during the use of this drug. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"842689"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31755803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preferential selectivity of inhibitors with human tau protein kinase gsk3β elucidates their potential roles for off-target Alzheimer's therapy.","authors":"Jagadeesh Kumar Dasappa,&nbsp;H G Nagendra","doi":"10.1155/2013/809386","DOIUrl":"https://doi.org/10.1155/2013/809386","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta peptides (Aβ) and neurofibrillary tangles (NFTs). The abnormal phosphorylation of tau leads to the formation of NFTs produced by the action of tau kinases, resulting in the loss of neurons and synapse, leading to dementia. Hence, tau kinases have become potential drug target candidates for small molecule inhibitors. With an aim to explore the identification of a common inhibitor, this investigation was undertaken towards analyzing all 10 tau kinases which are implicated in phosphorylation of AD. A set of 7 inhibitors with varied scaffolds were collected from the Protein Data Bank (PDB). The analysis, involving multiple sequence alignment, 3D structural alignment, catalytic active site overlap, and docking studies, has enabled elucidation of the pharmacophoric patterns for the class of 7 inhibitors. Our results divulge that tau protein kinases share a specific set of conserved structural elements for the binding of inhibitors and ATP, respectively. The scaffold of 3-aminopyrrolidine (inhibitor 6) exhibits high preferential affinity with GSK3β. Surprisingly, the PDB does not contain the structural details of GSK3β with this specific inhibitor. Thus, our investigations provide vital clues towards design of novel off-target drugs for Alzheimer's. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"809386"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/809386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31858329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular risk and hippocampal thickness in Alzheimer's disease.","authors":"Markus Donix, Maria Scharf, Kira Marschner, Annett Werner, Cathrin Sauer, Antje Gerner, Josef A Nees, Shirin Meyer, Katharina L Donix, Rüdiger Von Kummer, Vjera A Holthoff","doi":"10.1155/2013/108021","DOIUrl":"10.1155/2013/108021","url":null,"abstract":"<p><p>Cardiovascular risk factors influence onset and progression of Alzheimer's disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer's disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer's disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer's disease, and age did not influence cortical thickness. Alzheimer's disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer's disease. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"108021"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31863674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KIF6 719Arg Carrier Status Association with Homocysteine and C-Reactive Protein in Amnestic Mild Cognitive Impairment and Alzheimer's Disease Patients.","authors":"Michael Malek-Ahmadi,&nbsp;Amar Patel,&nbsp;Marwan N Sabbagh","doi":"10.1155/2013/242303","DOIUrl":"https://doi.org/10.1155/2013/242303","url":null,"abstract":"<p><p>Recent research has demonstrated associations between statin use, KIF6 719Arg carrier status, and cholesterol levels and amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) patients. The association between 719Arg carrier status with homocysteine (tHcy) and c-reactive protein (CRP) levels in aMCI and AD has not been previously investigated. Data from 175 aMCI and AD patients were used for the analysis. 719Arg carriers had significantly lower levels of tHcy than noncarriers (P = 0.02). No significant difference in CRP levels between 719Arg carriers and noncarriers was present (P = 0.37). Logistic regression yielded no significant effect for 719Arg status on CRP [OR = 1.79 (0.85, 3.83), P = 0.13] but did demonstrate a significant effect for tHcy [OR = 0.44 (0.23, 0.83), P = 0.01] after adjusting for ApoE ε4 carrier status, age, gender, and statin use. This study is the first to explore the relationship between KIF6 719Arg carrier status with tHcy and CRP levels. 719Arg carriers were more likely to have normal tHcy levels after adjusting for ApoE ε4 status, age, gender, and statin use. These results suggest that the KIF6 gene might influence cardiovascular pathways associated with AD. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"242303"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/242303","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32055766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Copper and/or Cholesterol Overload on Mitochondrial Function in a Rat Model of Incipient Neurodegeneration.","authors":"Nathalie Arnal, Omar Castillo, María J T de Alaniz, Carlos A Marra","doi":"10.1155/2013/645379","DOIUrl":"10.1155/2013/645379","url":null,"abstract":"<p><p>Copper (Cu) and cholesterol (Cho) are both associated with neurodegenerative illnesses in humans and animals models. We studied the effect in Wistar rats of oral supplementation with trace amounts of Cu (3 ppm) and/or Cho (2%) in drinking water for 2 months. Increased amounts of nonceruloplasmin-bound Cu were observed in plasma and brain hippocampus together with a higher concentration of ceruloplasmin in plasma, cortex, and hippocampus. Cu, Cho, and the combined treatment Cu + Cho were able to induce a higher Cho/phospholipid ratio in mitochondrial membranes with a simultaneous decrease in glutathione content. The concentration of cardiolipin decreased and that of peroxidation products, conjugated dienes and lipoperoxides, increased. Treatments including Cho produced rigidization in both the outer and inner mitochondrial membranes with a simultaneous increase in permeability. No significant increase in Cyt C leakage to the cytosol was observed except in the case of cortex from rats treated with Cu and Cho nor were there any significant changes in caspase-3 activity and the Bax/Bcl2 ratio. However, the A β (1-42)/(1-40) ratio was higher in cortex and hippocampus. These findings suggest an incipient neurodegenerative process induced by Cu or Cho that might be potentiated by the association of the two supplements. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"645379"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31977165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual screening and biological evaluation of piperazine derivatives as human acetylcholinesterase inhibitors.","authors":"Kavitha Raj Varadaraju,&nbsp;Jajur Ramanna Kumar,&nbsp;Lingappa Mallesha,&nbsp;Archana Muruli,&nbsp;Kikkeri Narasimha Shetty Mohana,&nbsp;Chethan Kumar Mukunda,&nbsp;Umesha Sharanaiah","doi":"10.1155/2013/653962","DOIUrl":"https://doi.org/10.1155/2013/653962","url":null,"abstract":"<p><p>The piperazine derivatives have been shown to inhibit human acetylcholinesterase. Virtual screening by molecular docking of piperazine derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K), 4-(4-methyl)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S1), and 4-(4-chloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S3) has been shown to bind at peripheral anionic site and catalytic sites, whereas 4-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S4) and 4-(2,5-dichloro)-benzenesulfonyl-1-(1,4-benzodioxane-2-carbonyl) piperazine (S7) do not bind either to peripheral anionic site or catalytic site with hydrogen bond. All the derivatives have differed in number of H-bonds and hydrophobic interactions. The peripheral anionic site interacting molecules have proven to be potential therapeutics in inhibiting amyloid peptides aggregation in Alzheimer's disease. All the piperazine derivatives follow Lipinski's rule of five. Among all the derivatives 1-(1,4-benzodioxane-2-carbonyl) piperazine (K) was found to have the lowest TPSA value. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"653962"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/653962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31911743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers in Alzheimer's disease and lewy body disorders with dementia.","authors":"Thomas Leyhe,&nbsp;Taher Darreh-Shori,&nbsp;Christoph Laske,&nbsp;Michelle M Mielke,&nbsp;Walter Maetzler","doi":"10.1155/2013/473181","DOIUrl":"https://doi.org/10.1155/2013/473181","url":null,"abstract":"The present special issue provides a synthesis of current materials and techniques used to not only explore, but also to validate and evaluate novel markers, potentially new biomarkers, in the field of dementias associated with Alzheimer's and Lewy body pathology. This topic is of particular interest as only a very minor proportion of potential markers detected in preclinical studies will ultimately be included in larger clinical studies or for routine clinical use.","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"473181"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/473181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31200868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper status in Alzheimer's disease and other neurodegenerative disorders 2013.","authors":"Rosanna Squitti,&nbsp;Tjaard Hoogenraad,&nbsp;George Brewer,&nbsp;Ashley I Bush,&nbsp;Renato Polimanti","doi":"10.1155/2013/838274","DOIUrl":"https://doi.org/10.1155/2013/838274","url":null,"abstract":"In recent years, the number of studies about the role of copper metabolism in the pathophysiology of Alzheimer's disease (AD) has been rapidly increasing. A wide range of experimental approaches have been used to explore this important issue: in vitro analyses, investigations on animal models, bioinformatic surveys, and patients' studies. Most of these studies have indicated that systemic disarrangements of copper metabolism can be one of the pathologic pathways at the basis of AD, and moreover, preventive and therapeutic strategies based on copper may be developed in order to slow down or to block the disease progression. However, further studies are necessary to translate these findings into clinical practice. In 2011, the International Journal of Alzheimer's Disease (IJAD) published the annual issue “Copper Status in Alzheimer's Disease and Other Neurodegenerative Disorders”, in order to collect some relevant studies about copper and AD. After two years, due to the growing literature about this topic, we and IJAD have decided to present the 2013 annual issue. In this issue, studies from different international authors are published about the recent advances in the field of copper metabolism in AD. We decided to include investigations based on different approaches in order to display the multiplicity of experimental methodologies, currently present to investigate this important subject. \u0000 \u0000One of the paper of this annual issue is a review article by B. G. Schreurs about the use of the AD rabbit model based on a 2% cholesterol diet to explore the role of copper in drinking water in determining the AD progression, especially highlighting the outstanding contribution of the late D. L. Sparks. \u0000 \u0000Another paper is provided by K. Singh and collaborators. They present novel data about the positive effects of a new copper chelator, L-2,6-pyridinedicarboxylic acid, 2,6-bis[2-[(4-carboxyphenyl) methylene] hydrazide], in the eye tissues of transgenic Drosophila expressing beta-amyloid (Aβ). \u0000 \u0000One of the paper is a review article by G. J. Brewer and S. Kaur about the importance of ingestion of inorganic copper (such as that of drinking water) as a possible factor of AD causation and of zinc therapy to reduce serum “free” copper levels and, consequently, to slow down cognition loss in AD patients. They also furnished novel data about a 6-month small double blind trial of a new zinc formulation on AD patients. \u0000 \u0000In another paper, A. Rembach and colleagues show their outcomes on the brain-specific alteration in copper levels of AD patients. Specifically, they observed that the decrease of copper in the human frontal cortex was confined in the soluble fractions. \u0000 \u0000Two of the papers are two research articles provided by N. Arnal and collaborators. In these papers, they display the interactions between copper and cholesterol in neurodegenerative processes of Wistar rats and the effects of copper and cholesterol on mitochondrial function in a rat model. \u0000 \u0000Ano","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"838274"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2013/838274","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32055767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc deficiency and zinc therapy efficacy with reduction of serum free copper in Alzheimer's disease.","authors":"George J Brewer, Sukhvir Kaur","doi":"10.1155/2013/586365","DOIUrl":"10.1155/2013/586365","url":null,"abstract":"<p><p>We are in the midst of an epidemic of Alzheimer's disease (AD) in developed countries. We have postulated that ingestion of inorganic copper from drinking water and taking supplement pills and a high fat diet are major causative factors. Ingestion of inorganic copper can directly raise the blood free copper level. Blood free copper has been shown by the Squitti group to be elevated in AD, to correlate with cognition, and to predict cognition loss. Secondly, we have shown that AD patients are zinc deficient compared to age matched controls. Zinc is important in neuronal protection. We carried out a 6-month small double blind trial of a new zinc formulation on AD patients. We found that in patients 70 years and older, zinc therapy protected against cognition decline compared to placebo controls. We also found that zinc therapy significantly lowered blood free copper levels. So zinc efficacy could be due to restoring neuronal zinc levels, to lowering blood free copper levels, or to both. </p>","PeriodicalId":13802,"journal":{"name":"International Journal of Alzheimer's Disease","volume":"2013 ","pages":"586365"},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31859398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}