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https://www.readbyqxmd.com/read/28346580/searching-for-neurodegeneration-in-the-blood-of-patients-with-alzheimer-disease
#1
Douglas Galasko
No abstract text is available yet for this article.
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28346578/association-of-plasma-neurofilament-light-with-neurodegeneration-in-patients-with-alzheimer-disease
#2
Niklas Mattsson, Ulf Andreasson, Henrik Zetterberg, Kaj Blennow
Importance: Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive or expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker for neurodegeneration in dementias. Objective: To test whether plasma NFL concentrations are increased in AD and associated with cognitive decline, other AD biomarkers, and imaging evidence of neurodegeneration...
March 27, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28346566/gene-gene-interaction-between-pparg-and-apoe-gene-on-late-onset-alzheimer-s-disease-a-case-control-study-in-chinese-han-population
#3
S Wang, L Guan, D Luo, J Liu, H Lin, X Li, X Liu
AIMS: The aim was to investigate the impact of PPARG and APOE gene single nucleotide polymorphisms (SNPs) and additional gene- gene interaction on late-onset Alzheimer's disease (LOAD) risk based on Chinese Han population. METHODS: A total of 928 participants (466 males, 462 females), with a mean age of 81.3 ± 16.4 years old, were included in the study, including 460 LOAD patients and 468 normal controls participants. Logistic regression was performed to investigate association between SNP and LOAD risk and generalized multifactor dimensionality reduction (GMDR) was used to analysis the gene-gene interaction...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28346565/anticholinergic-burden-and-functional-status-in-older-people-with-cognitive-impairment-results-from-the-regal-project
#4
V Boccardi, M Baroni, L Paolacci, S Ercolani, A Longo, M Giordano, C Ruggiero, P Mecocci
OBJECTIVE: The use of drugs with intrinsic anticholinergic properties is widespread among old age persons. A growing body of evidences suggest that a high anticholinergic burden is associated with physical and cognitive impairment. However, the association between anticholinergic drug use and functional status is still poorly investigated, particularly among subjects with initial cognitive impairment. DESIGN: Cross-sectional study examining the association between drug-related anticholinergic burden and functional status in cognitively healthy (CH) (n=691), mild cognitive impairment (MCI) (n=541) or mild Alzheimer's diseases (AD) (n=1127) subjects...
2017: Journal of Nutrition, Health & Aging
https://www.readbyqxmd.com/read/28346227/reducing-expression-of-synapse-restricting-protein-ephexin5-ameliorates-alzheimer-s-like-impairment-in-mice
#5
Gabrielle L Sell, Thomas B Schaffer, Seth S Margolis
Accumulation of amyloid-β (Aβ) protein may cause synapse degeneration and cognitive impairment in Alzheimer's disease (AD) by reactivating expression of the developmental synapse repressor protein Ephexin5 (also known as ARHGEF15). Here, we have reported that Aβ is sufficient to acutely promote the production of Ephexin5 in mature hippocampal neurons and in mice expressing human amyloid precursor protein (hAPP mice), a model for familial AD that produces high brain levels of Aβ. Ephexin5 expression was highly elevated in the hippocampi of human AD patients, indicating its potential relevance to AD...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#6
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345579/inhibition-of-delta-secretase-improves-cognitive-functions-in-mouse-models-of-alzheimer-s-disease
#7
Zhentao Zhang, Obiamaka Obianyo, Elfriede Dall, Yuhong Du, Haian Fu, Xia Liu, Seong Su Kang, Mingke Song, Shan-Ping Yu, Chiara Cabrele, Mario Schubert, Xiaoguang Li, Jian-Zhi Wang, Hans Brandstetter, Keqiang Ye
δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer's disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345494/adaptation-and-validation-of-the-alzheimer-s-disease-assessment-scale-cognitive-adas-cog-in-a-low-literacy-setting-in-sub-saharan-africa
#8
Stella-Maria Paddick, Aloyce Kisoli, Sarah Mkenda, Godfrey Mbowe, William Keith Gray, Catherine Dotchin, Adesola Ogunniyi, John Kisima, Olaide Olakehinde, Declare Mushi, Richard William Walker
OBJECTIVE: This study aimed to assess the feasibility of a low-literacy adaptation of the Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) for use in rural sub-Saharan Africa (SSA) for interventional studies in dementia. No such adaptations currently exist. METHODS: Tanzanian and Nigerian health professionals adapted the ADAS-Cog by consensus. Validation took place in a cross-sectional sample of 34 rural-dwelling older adults with mild/moderate dementia alongside 32 non-demented controls in Tanzania...
March 27, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28345017/proof-of-concept-demonstration-of-optimal-composite-mri-endpoints-for-clinical-trials
#9
Steven D Edland, M Colin Ard, Jaiashre Sridhar, Derin Cobia, Adam Martersteck, M Marsel Mesulam, Emily J Rogalski
BACKGROUND: Atrophy measures derived from structural MRI are promising outcome measures for early phase clinical trials, especially for rare diseases such as primary progressive aphasia (PPA), where the small available subject pool limits our ability to perform meaningfully powered trials with traditional cognitive and functional outcome measures. METHODS: We investigated a composite atrophy index in 26 PPA participants with longitudinal MRIs separated by two years...
September 2016: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/28344933/precision-medicine-the-golden-gate-for-detection-treatment-and-prevention-of-alzheimer-s-disease
#10
H Hampel, S E O'Bryant, J I Castrillo, C Ritchie, K Rojkova, K Broich, N Benda, R Nisticò, R A Frank, B Dubois, V Escott-Price, S Lista
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy...
December 2016: Journal of Prevention of Alzheimer's Disease
https://www.readbyqxmd.com/read/28344778/methodological-advances-in-imaging-intravital-axonal-transport
#11
REVIEW
James N Sleigh, Alessio Vagnoni, Alison E Twelvetrees, Giampietro Schiavo
Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer's disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation...
2017: F1000Research
https://www.readbyqxmd.com/read/28344552/adding-recognition-discriminability-index-to-the-delayed-recall-is-useful-to-predict-conversion-from-mild-cognitive-impairment-to-alzheimer-s-disease-in-the-alzheimer-s-disease-neuroimaging-initiative
#12
María J Russo, Jorge Campos, Silvia Vázquez, Gustavo Sevlever, Ricardo F Allegri
Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28344551/construction-and-analysis-of-weighted-brain-networks-from-sice-for-the-study-of-alzheimer-s-disease
#13
Jorge Munilla, Andrés Ortiz, Juan M Górriz, Javier Ramírez
Alzheimer's Disease (AD) is the most common neurodegenerative disease in elderly people, and current drugs, unfortunately, do not represent yet a cure but only slow down its progression. This is explained, at least in part, because the understanding of the neurodegenerative process is still incomplete, being sometimes mistaken, particularly at the first steps of the illness, with the natural aging process. A better identification of how the functional activity deteriorates is thus crucial to develop new and more effective treatments...
2017: Frontiers in Neuroinformatics
https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#14
REVIEW
Marcus O W Grimm, Janine Mett, Heike S Grimm, Tobias Hartmann
Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28344491/effect-of-aster-tataricus-on-production-of-inflammatory-mediators-in-lps-stimulated-rat-astrocytoma-cell-line-c6-and-thp-1-cells
#15
Hong-Tao Zhang, Miao Tian, Qiao-Wei He, Nan Chi, Chun-Ming Xiu, Yun-Bo Wang
Neuroinflammation is the commonest cause of neurodegenerative diseases such as Alzheimer's disease. Present investigation evaluates the inhibitory effect of ethanolic root extract of Aster tataricus (AS) on inflammatory mediators production in lipopolysaccharide (LPS) stimulated C6 cells. C6 cells were treated with AS (20 and 40 mg/kg) and nimesulide (NSL, 1.5 μg/ml) for 1 day. Thereafter various parameters such as production of ROS, release of nitrite, MDA, glutathione level and NF-κB translocation were estimated in C6 cell lines...
March 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344073/role-of-thrombin-par1-pkc%C3%AE-%C3%AE-axis-in-brain-pericytes-in-thrombin-induced-mmp-9-production-and-blood-brain-barrier-dysfunction-in-vitro
#16
Takashi Machida, Shinya Dohgu, Fuyuko Takata, Junichi Matsumoto, Ikuya Kimura, Mariko Koga, Keiko Nakamoto, Atsushi Yamauchi, Yasufumi Kataoka
Thrombin, an essential component in the coagulation cascade, participates in the pathogenesis of brain diseases, such as ischemic stroke, intracerebral hemorrhage, Alzheimer's disease and Parkinson's disease through blood-brain barrier (BBB) dysfunction. It is thought that the thrombin-matrix metalloproteinase (MMP)-9 axis is an important process in the pathogenesis of neurovascular disease, such as BBB dysfunction. We recently reported that brain pericytes are the most MMP-9-releasing cells in response to thrombin stimulation among the BBB-constituting cells...
March 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28343848/capillary-dysfunction-is-associated-with-symptom-severity-and-neurodegeneration-in-alzheimer-s-disease
#17
Rune B Nielsen, Lærke Egefjord, Hugo Angleys, Kim Mouridsen, Michael Gejl, Arne Møller, Birgitte Brock, Hans Brændgaard, Hanne Gottrup, Jørgen Rungby, Simon F Eskildsen, Leif Østergaard
INTRODUCTION: We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning. METHODS: Thirty-two AD patients underwent cognitive testing, structural magnetic resonance imaging (MRI), and perfusion MRI at baseline and after 6 months. We measured cortical thickness, microvascular cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and capillary transit time heterogeneity (CTH) and estimated tissue oxygen tension (PtO2)...
March 23, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28343297/association-of-the-cx3cr1-v249i-variant-with-neurofibrillary-pathology-progression-in-late-onset-alzheimer-s-disease
#18
Alan López-López, Ellen Gelpi, Diana Maria Lopategui, Jose M Vidal-Taboada
Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls)...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28343095/ion-mobility-mass-spectrometry-and-orthogonal-gas-phase-techniques-to-study-amyloid-formation-and-inhibition
#19
REVIEW
Waldemar Hoffmann, Gert von Helden, Kevin Pagel
Amyloidogenic peptide oligomers are responsible for a variety of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Due to their dynamic, polydisperse, and polymorphic nature, these oligomers are very challenging to characterize using traditional condensed-phase methods. In the last decade, ion mobility-mass spectrometry (IM-MS) and related gas-phase techniques have emerged as a powerful alternative to disentangle the structure and assembly characteristics of amyloid forming systems. This review highlights recent advances in which IM-MS was used to characterize amyloid oligomers and their underlying assembly pathway...
March 23, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#20
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 22, 2017: Behavioural Brain Research
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