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https://www.readbyqxmd.com/read/28535056/solid-state-nmr-structure-based-inhibitor-design-to-achieve-selective-inhibition-of-the-parallel-in-register-%C3%AE-sheet-versus-antiparallel-iowa-mutant-%C3%AE-amyloid-fibrils
#1
Qinghui Cheng, Wei Qiang
Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has been widely applied to characterize the high-resolution structures of β-amyloid (Aβ) fibrils. While these structures provide crucial molecular insights on the deposition of amyloid plaques in Alzheimer's diseases (AD), ssNMR structures have been rarely used so far as basis for designing inhibitors. It remains a challenge because the ssNMR-based Aβ fibrils structures were usually obtained with sparsely-isotope-labeled peptides with limited experimental constraints, where the structural models, especially the side-chain coordinates showed restricted precision...
May 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28534925/osmotin-loaded-magnetic-nanoparticles-with-electromagnetic-guidance-for-the-treatment-of-alzheimer-s-disease
#2
Faiz Ul Amin, Ali Kafash Hoshiar, Ton Duc Do, Yeongil Noh, Shahid Ali Shah, Muhammad Sohail Khan, Jungwon Yoon, Myeong Ok Kim
Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregated amyloid beta (Aβ) in the brain. Here, we describe for the first time the development of a new, pioneering nanotechnology-based drug delivery approach for potential therapies for neurodegenerative diseases, particularly AD. We demonstrated the delivery of fluorescent carboxyl magnetic Nile Red particles (FMNPs) to the brains of normal mice using a functionalized magnetic field (FMF) composed of positive- and negative-pulsed magnetic fields generated by electromagnetic coils...
May 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/28534798/alzheimer-s-disease-diagnosis-using-landmark-based-features-from-longitudinal-structural-mr-images
#3
Jun Zhang, Mingxia Liu, Le An, Yaozong Gao, Dinggang Shen
Structural magnetic resonance imaging (MRI) has been proven to be an effective tool for Alzheimer's disease (AD) diagnosis. While conventional MRI-based AD diagnosis typically uses images acquired at a single time point, a longitudinal study is more sensitive in detecting early pathological changes of AD, making it more favorable for accurate diagnosis. In general, there are two challenges faced in MRI-based diagnosis. First, extracting features from structural MR images requires timeconsuming nonlinear registration and tissue segmentation, whereas the longitudinal study with involvement of more scans further exacerbates the computational costs...
May 16, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28534796/predicting-progression-from-mild-cognitive-impairment-to-alzheimer-s-disease-using-autoregressive-modelling-of-longitudinal-and-multimodal-biomarkers
#4
Sidra Minhas, Aasia Khanum, Farhan Riaz, Shoab Khan, Atif Alvi
Mild Cognitive Impairment is a preclinical stage of Alzheimer's disease (AD). For effective treatment of AD, it is important to identify MCI patients who are at a high risk of developing AD over the course of time. İn this study, autoregressive modelling of multiple heterogeneous predictors of Alzheimer's dısease is performed to capture their evolution over time. The models are trained using three different arrangements of longitudinal data. These models are then used to estimate future biomarker readings of individual test subjects...
May 16, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28534760/minibrain-storm-cerebral-organoids-aren-t-real-brains-but-they-provide-a-powerful-platform-for-modeling-brain-diseases-like-zika-infection-alzheimer-s-and-even-autism
#5
Shannon Fischer
Floating in a Petri dish, they look like tiny tapioca pearls in peach broth, a couple dozen in number and none much larger than the tip of a ballpoint pen. But under a microscope, dense, lumpy bodies come into focus, outlined by wispy coronas.
May 2017: IEEE Pulse
https://www.readbyqxmd.com/read/28534735/the-use-of-the-gaps-in-noise-test-as-an-index-of-the-enhanced-left-temporal-cortical-thinning-associated-with-the-transition-between-mild-cognitive-impairment-and-alzheimer-s-disease
#6
Vasiliki Vivian Iliadou, Doris-Eva Bamiou, Christos Sidiras, Nikolaos P Moschopoulos, Magda Tsolaki, Ioannis Nimatoudis, Gail D Chermak
BACKGROUND: The known link between auditory perception and cognition is often overlooked when testing for cognition. PURPOSE: To evaluate auditory perception in a group of older adults diagnosed with mild cognitive impairment (MCI). RESEARCH DESIGN: A cross-sectional study of auditory perception. STUDY SAMPLE: Adults with MCI and adults with no documented cognitive issues and matched hearing sensitivity and age. DATA COLLECTION: Auditory perception was evaluated in both groups, assessing for hearing sensitivity, speech in babble (SinB), and temporal resolution...
May 2017: Journal of the American Academy of Audiology
https://www.readbyqxmd.com/read/28534696/light-sleep-and-circadian-rhythms-in-older-adults-with-alzheimer-s-disease-and-related-dementias
#7
Mariana G Figueiro
Alzheimer's disease and related dementias (ADRD) can cause sleep and behavioral problems that are problematic for ADRD patients and their family caregivers. Light therapy has shown promise as a nonpharmacological treatment, and preliminary studies demonstrate that timed light exposure can consolidate and improve nighttime sleep efficiency, increase daytime wakefulness and reduce evening agitation without the adverse effects of pharmacological solutions. Compliance with light treatment and the accurate measurement of light exposures during treatment, however, have presented barriers for the adoption of light therapy for ADRD...
May 23, 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/28534431/ameliorating-effect-of-anti-alzheimer-s-drugs-on-the-bidirectional-association-between-type-2-diabetes-mellitus-and-alzheimer-s-disease
#8
Amira S Ahmed, Rehab M Elgharabawy, Amal H Al-Najjar
Mild to severe forms of nervous system damage were exhibited by approximately 60-70% of diabetics. It is important to understand the association between type 2 diabetes mellitus and Alzheimer's disease. The aim of the present work is to understand the bidirectional association between type 2 diabetes and Alzheimer's disease pathogenesis, that was monitored by glycaemic status, lipid profile, amyloid beta 40 and 42 (Aβ40 and Aβ42), C-reactive protein, total creatine kinase, total lactate dehydrogenase, D-dimer and magnesium measurements, to assess the association between theses biochemical markers and each other, to estimate the possibility of utilizing the amyloid beta as biochemical marker of T2D in Alzheimer's patients, and to evaluate the effect of piracetam and memantine drugs on diabetes mellitus...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28534301/effects-of-acetyl-l-carnitine-in-diabetic-neuropathy-and-other-geriatric-disorders
#9
REVIEW
G Sergi, S Pizzato, F Piovesan, C Trevisan, N Veronese, E Manzato
A long history of diabetes mellitus and increasing age are associated with the onset of diabetic neuropathy, a painful and highly disabling complication with a prevalence peaking at 50% among elderly diabetic patients. Acetyl-L-carnitine (ALC) is a molecule derived from the acetylation of carnitine in the mitochondria that has an essential role in energy production. It has recently been proposed as a therapy to improve the symptoms of diabetic neuropathy. ALC is widely distributed in mammalian tissues, including the brain, blood-brain barrier, brain neurons, and astrocytes...
May 22, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28534084/the-emerging-link-between-o-glcnacylation-and-neurological-disorders
#10
REVIEW
Xiaofeng Ma, He Li, Yating He, Junwei Hao
O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28533891/nuclear-uptake-of-an-amino-terminal-fragment-of-apolipoprotein-e4-promotes-cell-death-and-localizes-within-microglia-of-the-alzheimer-s-disease-brain
#11
Julia E Love, Ryan J Day, Justin W Gause, Raquel J Brown, Xinzhu Pu, Dustin I Theis, Chad A Caraway, Wayne W Poon, Abir A Rahman, Brad E Morrison, Troy T Rohn
Although harboring the apolipoprotein E4 (APOE4) allele is a well known risk factor in Alzheimer's disease (AD), the mechanism by which it contributes to disease risk remains elusive. To investigate the role of proteolysis of apoE4 as a potential mechanism, we designed and characterized a site-directed cleavage antibody directed at position D151 of the mature form of apoE4 and E3. Characterization of this antibody indicated a high specificity for detecting synthesized recombinant proteins corresponding to the amino acid sequences 1-151 of apoE3 and E4 that would generate the 17 kDa (p17) fragment...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28533411/bidirectional-regulation-of-a%C3%AE-levels-by-presenilin-1
#12
Victor Bustos, Maria V Pulina, Yildiz Kelahmetoglu, Subhash C Sinha, Fred S Gorelick, Marc Flajolet, Paul Greengard
Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase is an intramembranous protein complex composed of Aph1, Pen2, Nicastrin, and Presenilin 1. Although it has a central role in the pathogenesis of AD, knowledge of the mechanisms that regulate PS1 function is limited...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533369/phosphorylated-presenilin-1-decreases-%C3%AE-amyloid-by-facilitating-autophagosome-lysosome-fusion
#13
Victor Bustos, Maria V Pulina, Ashley Bispo, Alison Lam, Marc Flajolet, Fred S Gorelick, Paul Greengard
Presenilin 1 (PS1), the catalytic subunit of the γ-secretase complex, cleaves βCTF to produce Aβ. We have shown that PS1 regulates Aβ levels by a unique bifunctional mechanism. In addition to its known role as the catalytic subunit of the γ-secretase complex, selective phosphorylation of PS1 on Ser367 decreases Aβ levels by increasing βCTF degradation through autophagy. Here, we report the molecular mechanism by which PS1 modulates βCTF degradation. We show that PS1 phosphorylated at Ser367, but not nonphosphorylated PS1, interacts with Annexin A2, which, in turn, interacts with the lysosomal N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vamp8...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533191/mir-34a-knockout-attenuates-cognitive-deficits-in-app-ps1-mice-through-inhibition-of-the-amyloidogenic-processing-of-app
#14
Chongdong Jian, Mengru Lu, Zhao Zhang, Long Liu, Xianfeng Li, Fang Huang, Ning Xu, Lina Qin, Qian Zhang, Donghua Zou
The noncoding miRNA-34a (miR-34a) is involved in Alzheimer's disease (AD) pathologenesis and shows potential for application as a biomarker for early diagnosis and intervention. Here, we established miR-34a knockout mice in an APP/PS1 background (APP/PS1-miR-34a KO mice) by crossbreeding miR-34a(-/-) mice with APP/PS1 mice. We then investigated cognitive impairment and related pathologies. The results showed that the level of miR-34a was increased at about 6months in APP/PS1 mice, consistent with the increase in amyloid β (Aβ), and cognitive function was significantly improved in mice when miR-34a was knocked out in 9-month-old and 12-month-old mice, indicating that miR-34a is a potential candidate for determining the progression of AD...
May 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/28533150/molecular-imaging-of-neuroinflammation-in-alzheimer-s-disease-and-mild-cognitive-impairment
#15
REVIEW
Dunja Knezevic, Romina Mizrahi
Neuroinflammatory changes have been demonstrated to be an important feature of Alzheimer's disease (AD), however; the exact role of neuroinflammation and its progression during disease is still not well understood. One of the main drivers of the neuroinflammatory process is microglial cells. Positron Emission Tomography allows for the quantification of microglial activation by labelling the Translocator Protein 18kDa (TSPO), which becomes overexpressed upon activation of microglial cells. Several radioligands have been designed to target TSPO and have been studied in-vivo in AD populations...
May 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28533046/-are-language-disorders-in-alzheimer-s-disease-simply-aphasia
#16
REVIEW
Cyril Hazif-Thomas, Philippe Thomas
Alzheimer's disease is accompanied by gradual aphasia, becoming more severe when the cognitive disorders are more marked. However, the quality of care provided to the patient can modulate the evolution of these language difficulties. Aphasia is linked to a human communication deficiency and can be limited by taking into account the phatic function of language to keep the channels of communication open.
May 2017: Soins. Gérontologie
https://www.readbyqxmd.com/read/28533045/-evaluation-of-the-animal-assisted-therapy-in-alzheimer-s-disease
#17
Clémence Quibel, Marie Bonin, Magalie Bonnet, Maryse Gaimard, France Mourey, Isabelle Moesch, Pierre Ancet
Animal-assisted therapy sessions have been set up in a protected unit for patients with a dementia-related syndrome. The aim is to measure the effects of animal-assisted therapy on behavioural disorders in daily life and care. The results obtained provided some interesting areas to explore and recommendations with a view to optimising the implementation of such a system.
May 2017: Soins. Gérontologie
https://www.readbyqxmd.com/read/28533043/-dementia-and-non-pharmacological-therapy-the-effectiveness-of-play
#18
Cédric Gueyraud, Marie Anaut, Stéphane Sanchez, Philippe Denormandie, Anthony Bathsavanis, Pierre Krolak-Salmon
A study was carried out to look into the effectiveness of play and the ways it can be used in the treatment of Alzheimer's disease. An intervention founded on the principal of a recreational setting, taking into account the choice of objects, the layout of the space and the role of the professional, could present itself as a form of therapeutic mediation adapted to this pathology. This study shows that play helps to reduce the behavioural problems of residents with Alzheimer's disease, and boosted their wellbeing and quality of life...
May 2017: Soins. Gérontologie
https://www.readbyqxmd.com/read/28533042/-social-and-mood-enhancement-benefits-of-a-cognitive-remediation-workshop
#19
Karine Auffret, Céline Jacolot
A workshop focused on memory aimed at people with degenerative diseases like Alzheimer's disease can evolve into a social-therapeutic group for people also suffering from mood disorders. Cognitive remediation is therefore orientated towards social-mood mediation.
May 2017: Soins. Gérontologie
https://www.readbyqxmd.com/read/28533041/-alzheimer-s-disease-and-training-for-carers-in-a-rural-region
#20
Marie-Laure Lecat, Frank Pizon, Cédric Kempf
Alzheimer's disease or related diseases constitute a major public health issue at the heart of the 2014-2019 plan for neurodegenerative diseases. Family carers, seeing to the day-to-day care of their loved ones, require support, particularly in rural regions. A study carried out of these carers sought to understand their perception of Alzheimer's disease, their role, and in what ways their training can help to reduce their physical and mental exhaustion in order to improve their quality of life.
May 2017: Soins. Gérontologie
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