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https://www.readbyqxmd.com/read/28230352/disease-modifying-effects-of-m1-muscarinic-acetylcholine-receptor-activation-in-an-alzheimer-s-disease-mouse-model
#1
Evan P Lebois, Jason P Schroeder, Thomas J Esparza, Thomas M Bridges, Craig W Lindsley, P Jeffrey Conn, David L Brody, John Scott Daniels, Allan I Levey
Alzheimer's Disease (AD) is the leading cause of dementia worldwide and currently no disease-modifying therapy is available to slow or prevent AD, underscoring the urgent need for neuroprotective therapies. Selective M1 muscarinic acetylcholine receptor (mAChR) activation is an attractive mechanism for AD therapy since M1 mediates key effects on memory, cognition, and behavior and has potential for disease-modifying effects on Aβ formation and tau phosphorylation. To validate M1 as a neuroprotective treatment target for AD, the M1-selective agonist, VU0364572, was chronically dosed to 5XFAD mice from a young age preceding Aβ pathology (2 months) to an age where these mice are known to display memory impairments (6 months)...
February 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28230276/dissection-of-regulatory-elements-during-direct-conversion-of-somatic-cells-into-neurons
#2
Tahereh Soleimani, Nafiseh Falsafi, Hossein Fallahi
A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28230058/macrophage-migration-inhibitory-factor-is-subjected-to-glucose-modification-and-oxidation-in-alzheimer-s-disease
#3
Omar Kassaar, Marta Pereira Morais, Suying Xu, Emily L Adam, Rosemary C Chamberlain, Bryony Jenkins, Tony James, Paul T Francis, Stephen Ward, Robert J Williams, Jean van den Elsen
Glucose and glucose metabolites are able to adversely modify proteins through a non-enzymatic reaction called glycation, which is associated with the pathology of Alzheimer's Disease (AD) and is a characteristic of the hyperglycaemia induced by diabetes. However, the precise protein glycation profile that characterises AD is poorly defined and the molecular link between hyperglycaemia and AD is unknown. In this study, we define an early glycation profile of human brain using fluorescent phenylboronate gel electrophoresis and identify early glycation and oxidation of macrophage migration inhibitory factor (MIF) in AD brain...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228567/prolonged-sleep-duration-as-a-marker-of-early-neurodegeneration-predicting-incident-dementia
#4
Andrew J Westwood, Alexa Beiser, Nikita Jain, Jayandra J Himali, Charles DeCarli, Sanford H Auerbach, Matthew P Pase, Sudha Seshadri
OBJECTIVE: To evaluate the association between sleep duration and the risk of incident dementia and brain aging. METHODS: Self-reported total hours of sleep were examined in the Framingham Heart Study (n = 2,457, mean age 72 ± 6 years, 57% women) as a 3-level variable: <6 hours (short), 6-9 hours (reference), and >9 hours (long), and was related to the risk of incident dementia over 10 years, and cross-sectionally to total cerebral brain volume (TCBV) and cognitive performance...
February 22, 2017: Neurology
https://www.readbyqxmd.com/read/28227395/impaired-episodic-memory-network-in-subjects-at-high-risk-for-alzheimer-s-disease
#5
Yafeng Zhan, Jianhua Ma, Kaibin Xu, Yanhui Ding, Yue Cui, Zhengyi Yang, Yong Liu, Yafeng Zhan, Jianhua Ma, Kaibin Xu, Yanhui Ding, Yue Cui, Zhengyi Yang, Yong Liu, Yanhui Ding, Kaibin Xu, Yue Cui, Yafeng Zhan, Jianhua Ma, Zhengyi Yang, Yong Liu
Episodic memory dysfunction is one of the hallmark symptoms of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This cognitive impairment may be related to abnormal brain structure and activity. Functional connectivity mapping (FCM) analysis provides a powerful tool for exploring the topology of human brain function using magnetic resonance imaging (MRI). Thus, it would be advantageous to investigate the changes in functional connectivity within the episodic memory network in a longitudinal MCI dataset, as it may be helpful in identifying a potential marker of disease progress...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227007/identification-of-blood-biomarkers-for-use-in-point-of-care-diagnosis-tool-for-alzheimer-s-disease
#6
E Jammeh, P Zhao, C Carroll, S Pearson, E Ifeachor, E Jammeh, P Zhao, C Carroll, S Pearson, E Ifeachor, C Carroll, E Jammeh, E Ifeachor, S Pearson, P Zhao
Early diagnosis of Alzheimer's Disease (AD) is widely regarded as necessary to allow treatment to be started before irreversible damage to the brain occur and for patients to benefit from new therapies as they become available. Low-cost point-of-care (PoC) diagnostic tools that can be used to routinely diagnose AD in its early stage would facilitate this, but such tools require reliable and accurate biomarkers. However, traditional biomarkers for AD use invasive cerebrospinal fluid (CSF) analysis and/or expensive neuroimaging techniques together with neuropsychological assessments...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226665/changes-in-the-eeg-amplitude-as-a-biomarker-for-early-detection-of-alzheimer-s-disease
#7
Ali H Al-Nuaimi, Emmanuel Jammeh, Lingfen Sun, Emmanuel Ifeachor, Ali H Al-Nuaimi, Emmanuel Jammeh, Lingfen Sun, Emmanuel Ifeachor, Emmanuel Jammeh, Lingfen Sun, Ali H Al-Nuaimi, Emmanuel Ifeachor
The rapid increase in the number of older people with Alzheimer's disease (AD) and other forms of dementia represents one of the major challenges to the health and social care systems. Early detection of AD makes it possible for patients to access appropriate services and to benefit from new treatments and therapies, as and when they become available. The onset of AD starts many years before the clinical symptoms become clear. A biomarker that can measure the brain changes in this period would be useful for early diagnosis of AD...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225789/non-melanoma-skin-cancer-and-risk-of-alzheimer-s-disease-and-all-cause-dementia
#8
Sigrun A J Schmidt, Anne G Ording, Erzsébet Horváth-Puhó, Henrik T Sørensen, Victor W Henderson
Cancer patients may be at decreased risk of Alzheimer's disease. This hypothesis is best developed for non-melanoma skin cancer (NMSC), but supportive epidemiological data are sparse. We therefore conducted a nationwide cohort study of the association between NMSC and Alzheimer's disease (main outcome) and all-cause dementia. Using Danish medical databases, we identified adults diagnosed with NMSC between 1 January 1980 and 30 November 2013 (n = 216,221) and a comparison cohort of five individuals matched to each NMSC patient by sex and birth year (n = 1,081,097)...
2017: PloS One
https://www.readbyqxmd.com/read/28223932/cerebrospinal-fluid-levels-of-amyloid-beta-1-43-mirror-1-42-in-relation-to-imaging-biomarkers-of-alzheimer-s-disease
#9
Ina S Almdahl, Camilla Lauridsen, Per Selnes, Lisa F Kalheim, Christopher Coello, Beata Gajdzik, Ina Møller, Marianne Wettergreen, Ramune Grambaite, Atle Bjørnerud, Geir Bråthen, Sigrid B Sando, Linda R White, Tormod Fladby
Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer's disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer's disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer's disease has never been assessed...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28223920/therapeutic-potential-of-secreted-amyloid-precursor-protein-apps%C3%AE
#10
REVIEW
Bruce G Mockett, Max Richter, Wickliffe C Abraham, Ulrike C Müller
Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28223918/rpph1-upregulates-cdc42-expression-and-promotes-hippocampal-neuron-dendritic-spine-formation-by-competing-with-mir-330-5p
#11
Yifei Cai, Ziling Sun, Huizhen Jia, Hongxue Luo, Xiaoyang Ye, Qi Wu, Yi Xiong, Wei Zhang, Jun Wan
Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. Recent studies employing microRNA-seq and genome-wide sequencing have identified some non-coding RNAs that are influentially involved in AD pathogenesis. Non-coding RNAs can compete with other endogenous RNAs by microRNA response elements (MREs) and manipulate biological processes, such as tumorigenesis. However, only a few non-coding RNAs have been reported in the pathogenesis of AD. In this study, we constructed the first competing endogenous RNA (ceRNA) network leveraging whole transcriptome sequencing and a previously studied microRNA-seq of APPswe/PS1ΔE9 transgenic mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28223916/the-emerging-roles-of-early-protein-folding-events-in-the-secretory-pathway-in-the-development-of-neurodegenerative-maladies
#12
REVIEW
Tatyana Dubnikov, Ehud Cohen
Although, protein aggregation and deposition are unifying features of various neurodegenerative disorders, recent studies indicate that different mechanisms can lead to the development of the same malady. Among these, failure in early protein folding and maturation emerge as key mechanistic events that lead to the manifestation of a myriad of illnesses including Alzheimer's disease and prion disorders. Here we delineate the cascade of maturation steps that nascent polypeptides undergo in the secretory pathway to become functional proteins, and the chaperones that supervise and assist this process, focusing on the subgroup of proline cis/trans isomerases...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28223022/early-identification-of-mild-cognitive-impairment-using-incomplete-random-forest-robust-support-vector-machine-and-fdg-pet-imaging
#13
Shen Lu, Yong Xia, Weidong Cai, Michael Fulham, David Dagan Feng
Alzheimer's disease (AD) is the most common type of dementia and will be an increasing health problem in society as the population ages. Mild cognitive impairment (MCI) is considered to be a prodromal stage of AD. The ability to identify subjects with MCI will be increasingly important as disease modifying therapies for AD are developed. We propose a semi-supervised learning method based on robust optimization for the identification of MCI from [18F]Fluorodeoxyglucose PET scans. We extracted three groups of spatial features from the cortical and subcortical regions of each FDG-PET image volume...
February 7, 2017: Computerized Medical Imaging and Graphics: the Official Journal of the Computerized Medical Imaging Society
https://www.readbyqxmd.com/read/28222527/gene-expression-and-methylation-analysis-of-abca7-in-patients-with-alzheimer-s-disease
#14
Kiyohiro Yamazaki, Yuta Yoshino, Takaaki Mori, Taku Yoshida, Yuki Ozaki, Tomoko Sao, Yoko Mori, Shinichiro Ochi, Jun-Ichi Iga, Shu-Ichi Ueno
BACKGROUND/OBJECTIVE: The aim of this study was to examine the blood gene expression and methylation of ATP-binding cassette sub-family A member 7 gene (ABCA7) as a biological marker of AD. METHODS: AD subjects (n = 50; 11 males, 77.7±6.05 years old) and age- and sex-matched healthy controls (n = 50) were recruited. A single nucleotide polymorphism in ABCA7 (rs3764650), methylation rates of CpG sites in the ABCA7 promoter region, and ABCA7 mRNA expression levels in peripheral blood were examined...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222508/chronic-lithium-treatment-in-a-rat-model-of-basal-forebrain-cholinergic-depletion-effects-on-memory-impairment-and-neurodegeneration
#15
Francesca Gelfo, Debora Cutuli, Annalisa Nobili, Paola De Bartolo, Marcello D'Amelio, Laura Petrosini, Carlo Caltagirone
Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28222369/what-can-gait-tell-us-about-dementia-review-of-epidemiological-and-neuropsychological-evidence
#16
REVIEW
Vyara Valkanova, Klaus P Ebmeier
BACKGROUND: Cognitive impairment and gait disorders in people over the age of 65 represent major public health issues because of their high frequency, their link to poor outcomes and high costs. Research has demonstrated that these two geriatric syndromes are closely related. METHODS AND RESULTS: We aim to review the evidence supporting the relationship between gait and cognitive impairment, particularly focusing on epidemiological and neuropsychological studies in patients with Mild cognitive impairment, Alzheimer's disease and Vascular dementia...
February 9, 2017: Gait & Posture
https://www.readbyqxmd.com/read/28219440/tau-pet-imaging-present-and-future-directions
#17
REVIEW
Laure Saint-Aubert, Laetitia Lemoine, Konstantinos Chiotis, Antoine Leuzy, Elena Rodriguez-Vieitez, Agneta Nordberg
Abnormal aggregation of tau in the brain is a major contributing factor in various neurodegenerative diseases. The role of tau phosphorylation in the pathophysiology of tauopathies remains unclear. Consequently, it is important to be able to accurately and specifically target tau deposits in vivo in the brains of patients. The advances of molecular imaging in the recent years have now led to the recent development of promising tau-specific tracers for positron emission tomography (PET), such as THK5317, THK5351, AV-1451, and PBB3...
February 20, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28219319/biomarkers-in-alzheimer-s-disease-recent-update
#18
Sushil Sharma, Walter Lipincott
Alzheimer disease (AD) is an age-related neurodegenerative disorder, characterized by loss of memory and cognitive function. It is the common cause of dementia in elderly and is a global health concern as the population of people aged 85 and older, is growing alarmingly. Although pharmacotherapy for the treatment of AD has improved, lot of work remains to treat this devastating disease. AD pathology begins even before the onset of clinical symptoms. Because therapies could be more effective if implemented early in the disease progression, it is highly prudent to discover reliable biomarkers, to detect its exact pathophysiology during pre-symptomatic stage...
February 20, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28218884/blood-brain-barrier-leakage-in-early-alzheimer-disease
#19
Augustin Lecler, Laure Fournier, Capucine Diard-Detoeuf, Daniel Balvay
No abstract text is available yet for this article.
March 2017: Radiology
https://www.readbyqxmd.com/read/28218850/impact-of-phosphorylation-and-pseudo-phosphorylation-on-the-early-stages-of-aggregation-of-the-microtubule-associated-protein-tau
#20
Dmitriy V Prokopovich, John W Whittaker, Micaiah M Muthee, Azka Ahmed, Luca Larini
The microtubule associated protein tau regulates the stability of microtubules within neurons in the central nervous system. In turn, microtubules are responsible for the remodeling of the cytoskeleton that ultimately leads to the formation or pruning of new connections among neurons. As a consequence, dysfunction of tau is associated with many forms of dementia as well as Alzheimer's disease. In the brain, tau activity is regulated by its phosphorylation state. Phosphorylation is a post-translational modification of proteins that adds a phosphate group to the side chain of an amino acid...
February 20, 2017: Journal of Physical Chemistry. B
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