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Barbara Hanratty, Daniel Stow, Danni Collingridge Moore, Nicole K Valtorta, Fiona Matthews
Background: loneliness has an adverse effect on health and well-being, and is common at older ages. Evidence that it is a risk factor for care home admission is sparse. Objective: to investigate the association between loneliness and care home admission. Setting: English Longitudinal Study of Ageing (ELSA). Participants: two-hundred fifty-four individuals across seven waves (2002-15) of ELSA who moved into care homes were age, sex matched to four randomly selected individuals who remained in the community...
July 10, 2018: Age and Ageing
Grazia Rutigliano, Martina Stazi, Ottavio Arancio, D Martin Watterson, Nicola Origlia
Neuroinflammation is a fundamental mechanism in Alzheimer's disease (AD) progression. The stress-induced activation of the p38α mitogen-activated protein kinase (MAPK) leads to increased production of proinflammatory cytokines and neurodegeneration. We investigated the effects of an isoform selective p38α MAPK inhibitor, MW01-18-150SRM (MW150), administered at 2.5 mg/kg/d (i.p.; 14 days) on early entorhinal cortex (EC) alterations in an AD mouse model carrying human mutations of the amyloid precursor protein (mhAPP)...
June 12, 2018: Neurobiology of Aging
Shino Magaki, Zhaoyi Tang, Spencer Tung, Christopher K Williams, Darrick Lo, William H Yong, Negar Khanlou, Harry V Vinters
Cerebral amyloid angiopathy (CAA), in which amyloid accumulates predominantly in the walls of arterioles and capillaries, is seen in most patients with Alzheimer disease (AD) and may contribute to compromise of blood-brain barrier (BBB) function seen in AD. We investigated the effects of CAA on BBB integrity by examining the expression of the endothelial marker CD31, basement membrane protein collagen IV (COL4), tight junction protein claudin-5, and fibrinogen, a marker of BBB leakage, by immunohistochemistry in the occipital cortex of autopsy brains with AD and capillary CAA (CAA type 1; n = 8), AD with noncapillary CAA (CAA type 2; n = 10), and AD without CAA (n = 7) compared with elderly controls (n = 10)...
June 11, 2018: Neurobiology of Aging
Claudia Balducci, Giulia Santamaria, Pietro La Vitola, Edoardo Brandi, Federica Grandi, Arturo Roberto Viscomi, Marten Beeg, Marco Gobbi, Mario Salmona, Simone Ottonello, Gianluigi Forloni
β-Amyloid oligomers (AβOs) and neuroinflammation are 2 main culprits to counteract in Alzheimer's disease (AD). Doxycycline (DOXY) is a second generation antibiotic of the tetracycline class that are promising drugs tested in many clinical trials for a number of different pathologies. DOXY is endowed with antiamyloidogenic properties and better crosses the blood-brain barrier, but its efficacy has never been tested in AD mice. We herein show that 15- to 16-month-old APP/PS1dE9 (APP/PS1) AD mice receiving DOXY under different treatment regimens recovered their memory without plaque reduction...
June 12, 2018: Neurobiology of Aging
Nicholas J Ashton, Mark Ide, Michael Schöll, Kaj Blennow, Simon Lovestone, Abdul Hye, Henrik Zetterberg
There is a need for an accessible biomarker that can complement current cerebrospinal fluid and imaging biomarkers in an accurate and early diagnosis of Alzheimer disease (AD). Saliva is a rich source of potential biomarkers and proteins related to neurodegenerative disorders have been shown to be present in this matrix, including tau. In this study, we quantified salivary total tau (t-tau) concentration in 160 healthy elderly control, 68 mild cognitive impairment, and 53 AD participants using ultrasensitive Single molecule array (Simoa) technology...
June 20, 2018: Neurobiology of Aging
Yumi Yamaguchi-Kabata, Takashi Morihara, Tomoyuki Ohara, Toshiharu Ninomiya, Atsushi Takahashi, Hiroyasu Akatsu, Yoshio Hashizume, Noriyuki Hayashi, Daichi Shigemizu, Keith A Boroevich, Manabu Ikeda, Michiaki Kubo, Masatoshi Takeda, Tatsuhiko Tsunoda
Alzheimer's disease (AD) is a common neurological disease that causes dementia in humans. Although the reports of associated pathological genes have been increasing, the molecular mechanism leading to the accumulation of amyloid-β (Aβ) in human brain is still not well understood. To identify novel genes that cause accumulation of Aβ in AD patients, we conducted an integrative analysis by combining a human genetic association study and transcriptome analysis in mouse brain. First, we examined genome-wide gene expression levels in the hippocampus, comparing them to amyloid Aβ level in mice with mixed genetic backgrounds...
July 13, 2018: Human Genetics
Soumya Sagar, Jonathan Rick, Ankush Chandra, Garima Yagnik, Manish K Aghi
Functional brain mapping (FBM) is an integral part of contemporary neurosurgery. It is crucial for safe and optimal resection of brain lesions like gliomas. The eloquent regions of the cortex like motor, somatosensory, Wernicke's, and Broca are usually mapped, either preoperatively or intraoperatively. Since its birth in the nineteenth century, FBM has witnessed immense modernization, radical refinements, and the introduction of novel techniques, most of which are non-invasive. Direct electrical stimulation of the cortex, despite its high invasiveness, remains the technique of choice...
July 13, 2018: Neurosurgical Review
Nare Torosyan, Chakmeedaj Sethanandha, Joshua D Grill, Michelle L Dilley, Jooyeon Lee, Jeffrey L Cummings, Celine Ossinalde, Daniel H Silverman
BACKGROUND: Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD...
July 10, 2018: Experimental Gerontology
Gui-Xiang Yang, Song-Lan Ge, Yan Wu, Jin Huang, Shi-Liang Li, Rui Wang, Lei Ma
A series of multifunctional 3-piperazinecarboxylate sarsasapogenin derivatives were designed and synthesized against Alzheimer's disease (AD). The protection against H2 O2 -triggered oxidative stress in PC12 cells, and inhibition on LPS-induced NO production in RAW264.7 cell lines in vitro by these derivatives were firstly evaluated. Most of the compounds showed better antioxidant and antiinflammatory activities compared with sarsasapogenin, especially AA34 and AA36. Structure-activity relationships revealed that benzyl group, electron-donating group and intramolecular hydrogen bond might be beneficial to enhancing their neuroprotective activities...
May 1, 2018: European Journal of Medicinal Chemistry
Domenico Cieri, Mattia Vicario, Francesca Vallese, Beatrice D'Orsi, Paola Berto, Alessandro Grinzato, Cristina Catoni, Diego De Stefani, Rosario Rizzuto, Marisa Brini, Tito Calì
Intracellular neurofibrillary tangles (NFT) composed by tau and extracellular amyloid beta (Aβ) plaques accumulate in Alzheimer's disease (AD) and contribute to neuronal dysfunction. Mitochondrial dysfunction and neurodegeneration are increasingly considered two faces of the same coin and an early pathological event in AD. Compelling evidence indicates that tau and mitochondria are closely linked and suggests that tau-dependent modulation of mitochondrial functions might be a trigger for the neurodegeneration process; however, whether this occurs either directly or indirectly is not clear...
July 10, 2018: Biochimica et Biophysica Acta
Quentin Lenoble, Xavier Corveleyn, Sébastien Szaffarczyk, Florence Pasquier, Muriel Boucart
AIM: Object/background association is critical to understand the context of visual scenes but also in daily life tasks like object search. Patients with Alzheimer disease (AD) exhibit impairment in scene processing at different levels: perception, recognition, memory and spatial navigation. We explored whether patients with AD make use of contextual information in congruent and incongruent target/background conditions in three different saccadic choice tasks. EXPERIMENT: We recruited 36 participants (12 young, 12 patients with AD at a moderate stage and 12 age-matched controls)...
June 20, 2018: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
Alice Mason, Clive Holmes, Christopher J Edwards
Dementia is a major international public health problem which looks set to grow as the ageing population increases. Despite large amounts of investment there has been relatively little progress in developing new therapies to combat this. There is a growing body of evidence that both local and systemic inflammation are important in dementia; with cerebral inflammation occurring secondarily to beta-amyloid plaques, raised levels of serum inflammatory molecules and cytokines being present in Alzheimer's disease patients and systemic inflammation being associated with cerebral microvasculature disease in vascular dementia...
July 10, 2018: Autoimmunity Reviews
Mirta Borin, Claudia Saraceno, Marcella Catania, Erika Lorenzetto, Valeria Pontelli, Anna Paterlini, Silvia Fostinelli, Anna Avesani, Giuseppe Di Fede, Gianluigi Zanusso, Luisa Benussi, Giuliano Binetti, Simone Zorzan, Roberta Ghidoni, Mario Buffelli, Silvia Bolognin
One of the earliest pathological features characterizing Alzheimer's disease (AD) is the loss of dendritic spines. Among the many factors potentially mediating this loss of neuronal connectivity, the contribution of Rho-GTPases is of particular interest. This family of proteins has been known for years as a key regulator of actin cytoskeleton remodeling. More recent insights have indicated how its complex signaling might be triggered also in pathological conditions. Here, we showed that the Rho-GTPase family member Rac1 levels decreased in the frontal cortex of AD patients compared to non-demented controls...
July 13, 2018: Acta Neuropathologica Communications
Krystal Herline, Eleanor Drummond, Thomas Wisniewski
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by protein aggregates of amyloid β (Aβ) and tau. These proteins have normal physiological functions, but in AD they undergo a conformational change and aggregate as toxic oligomeric and fibrillar species with a high β-sheet content. Areas covered: Active and passive immunotherapeutic approaches are among the most attractive methods for targeting misfolded Aβ and tau. Promising preclinical testing of various immunotherapeutic approaches have yet to translate to cognitive benefits in human clinical trials...
July 13, 2018: Expert Review of Vaccines
Sean M Cascarina, Kacy R Paul, Satoshi Machihara, Eric D Ross
Enhanced protein aggregation and/or impaired clearance of aggregates can lead to neurodegenerative disorders such as Alzheimer's Disease, Huntington's Disease, and prion diseases. Therefore, many protein quality control factors specialize in recognizing and degrading aggregation-prone proteins. Prions, which generally result from self-propagating protein aggregates, must therefore evade or outcompete these quality control systems in order to form and propagate in a cellular context. We developed a genetic screen in yeast that allowed us to explore the sequence features that promote degradation versus aggregation of a model glutamine/asparagine (Q/N)-rich prion domain from the yeast prion protein, Sup35, and two model glycine (G)-rich prion-like domains from the human proteins hnRNPA1 and hnRNPA2...
July 13, 2018: PLoS Genetics
Mustafa Sertbas, Kutlu O Ulgen
Neurology research and clinical practice are transforming toward postgenomics integrative biology. One such example is the study of human brain metabolism that is highly sophisticated due to reactions occurring in and between the astrocytes and neurons. Because of the inherent difficulty of performing experimental studies in human brain, metabolic network modeling has grown in importance to decipher the contribution of brain metabolite kinetics to human health and disease. Multiomics system science-driven metabolic models, using genome-scale and transcriptomics Big Data, offer the promise of new insights on metabolic networks in human brain...
July 2018: Omics: a Journal of Integrative Biology
Bingqing Shui, Dan Tao, Jing Cheng, Yong Mei, Nicole Jaffrezic-Renault, Zhenzhong Guo
Tau protein plays a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the assay to detect low concentrations of tau protein is a great challenge for the early diagnosis of AD. We will outline a novel aptamer-antibody sandwich assay based on an electrochemical biosensor for the detection of tau-381 in human serum. To improve the detection sensitivity, the aptamer-antibody sandwich assay for the detection of tau-381 was developed by using a tau antibody (anti-tau) and an aptamer specific to tau-381 as the recognition element and cysteamine-stabilized gold nanoparticles (AuNPs) for signal amplification...
July 13, 2018: Analyst
Mihaela-Liliana Tintas, Rabah Azzouz, Ludovic Peauger, Vincent Gembus, Emilie Petit, Laetitia Bailly, Cyril Papamicaël, Vincent Levacher
This work aims at exploiting both the enantioselective Tsuji allylation of allyl carbonate 6 and an organocatalytic aza-ene-type domino reaction between enal 3a and β-enaminone 4a to develop a straightforward access to all of the four possible stereoisomers of a donepezil-like 1,4-dihydropyridine 1a (er up to 99.5:0.5; overall yield up 64%); an anti-Alzheimer prodrug candidate. This strategy was extended to the preparation of other enantioenriched 1,4-dihydropyridines 1b-i (8 examples), highlighting its potential in the development of these chiral AChE inhibitors...
July 13, 2018: Journal of Organic Chemistry
Jelena Borovac, Miquel Bosch, Kenichi Okamoto
Activity-dependent plasticity of synaptic structure and function plays an essential role in neuronal development and in cognitive functions including learning and memory. The formation, maintenance and modulation of dendritic spines are mainly controlled by the dynamics of actin filaments (F-actin) through interaction with various actin-binding proteins (ABPs) and postsynaptic signaling messengers. Induction of long-term potentiation (LTP) triggers a cascade of events involving Ca2+ signaling, intracellular pathways such as cAMP and cGMP, and regulation of ABPs such as CaMKII, Cofilin, Aip1, Arp2/3, α-actinin, Profilin and Drebrin...
July 9, 2018: Molecular and Cellular Neurosciences
Ewa Niechwiej-Szwedo, Anthony Tapper, David Gonzalez, Ryan M Bradley, Robin Duncan
The apolipoprotein E (APOE) epsilon 4 isoform has been associated with a significantly greater risk of developing late onset Alzheimer's disease (AD). However, the negative effects of APOE-ε4 allele on cognitive function vary across the lifespan: reduced memory and executive function have been found in older individuals but, paradoxically, young APOE-ε4 carriers perform better on cognitive tests and show higher neural efficiency. This study aimed to assess the association between APOE genotype and saccade latency using a prosaccade and antisaccade task in young individuals (N = 97, age: 17-35 years)...
July 9, 2018: Behavioural Brain Research
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