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Alzheimers and obesity

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https://www.readbyqxmd.com/read/29223769/obstructive-sleep-apnoea-and-alzheimer-s-disease-in-search-of-shared-pathomechanisms
#1
REVIEW
D Polsek, N Gildeh, D Cash, R Winsky-Sommerer, S C R Williams, F Turkheimer, G D Leschziner, M J Morrell, I Rosenzweig
Alzheimer's disease (AD) is a significant public health concern. The incidence continues to rise, and it is set to be over one million in the UK by 2025. The processes involved in the pathogenesis of AD have been shown to overlap with those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA). Currently, the standard treatment for OSA is Continuous Positive Airway Pressure. Adherence to treatment can, however, be an issue, especially in patients with dementia. Also, not all patients respond adequately, necessitating the use of additional treatments...
December 6, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29217819/association-between-serum-neuron-specific-enolase-age-overweight-and-structural-mri-patterns-in-901-subjects
#2
Johanna Hoffmann, Deborah Janowitz, Sandra Van der Auwera, Katharina Wittfeld, Matthias Nauck, Nele Friedrich, Mohamad Habes, Christos Davatzikos, Jan Terock, Martin Bahls, Annemarie Goltz, Angela Kuhla, Henry Völzke, Hans Jörgen Grabe
Serum neuron-specific enolase (sNSE) is considered a marker for neuronal damage, related to gray matter structures. Previous studies indicated its potential as marker for structural and functional damage in conditions with adverse effects to the brain like obesity and dementia. In the present study, we investigated the putative association between sNSE levels, body mass index (BMI), total gray matter volume (GMV), and magnetic resonance imaging-based indices of aging as well as Alzheimer's disease (AD)-like patterns...
December 8, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29215310/apolipoprotein-e4-mediates-insulin-resistance-associated-cerebrovascular-dysfunction-and-the-post-prandial-response
#3
Lance A Johnson, Eileen Ruth Torres, Sydney Weber Boutros, Esha Patel, Tunde Akinyeke, Nabil J Alkayed, Jacob Raber
Metabolic dysfunction, commonly a result of diets high in saturated fats and sugar, is associated with impaired cognitive function and an increased risk of age-related cognitive decline (ACD) and Alzheimer's disease (AD). Compared to the E3 isoform of apolipoprotein (apoE), the E4 isoform is a major genetic risk factor for ACD, AD, and for developing cognitive impairments following various environmental challenges, including dietary challenges such as a high-fat diet (HFD). Both insulin resistance (IR) and E4 are associated with metabolic and vascular impairments...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29164610/shared-pathological-pathways-of-alzheimer-s-disease-with-specific-comorbidities-current-perspectives-and-interventions
#4
REVIEW
Christiane M Nday, Despoina Eleftheriadou, Graham Jackson
Alzheimer's disease (AD) belongs to one of the most multifactorial, complex and heterogeneous morbidity-leading disorders. Despite the extensive research in the field, AD pathogenesis is still at some extend obscure. Mechanisms linking AD with certain comorbidities, namely diabetes mellitus, obesity and dyslipidemia, are increasingly gaining importance, mainly due to their potential role in promoting AD development and exacerbation. Their exact cognitive impairment trajectories, however, remain to be fully elucidated...
November 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29164373/the-possible-factors-affecting-microglial-activation-in-cases-of-obesity-with-cognitive-dysfunction
#5
REVIEW
Titikorn Chunchai, Nipon Chattipakorn, Siriporn C Chattipakorn
Obesity has reached epidemic proportions in many countries around the world. Several studies have reported that obesity can lead to the development of cognitive decline. There is increasing evidence to demonstrate that microglia play a crucial role in cognitive decline in cases of obesity, Alzheimer's disease and also in the aging process. Although there have been several studies into microglia over the past decades, the mechanistic link between microglia and cognitive decline in obese models is still not fully understood...
November 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29163489/ameliorating-amyloid-%C3%AE-fibrils-triggered-inflammation-via-curcumin-loaded-polymeric-nanoconstructs
#6
Andrea Ameruoso, Roberto Palomba, Anna Lisa Palange, Antonio Cervadoro, Aeju Lee, Daniele Di Mascolo, Paolo Decuzzi
Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer's disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs) and 1,000 nm discoidal polymeric nanoconstructs (DPNs) were synthesized using poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and lipid chains as building blocks...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163128/insulin-resistance-and-alzheimer-s-disease-bioenergetic-linkages
#7
REVIEW
Bryan J Neth, Suzanne Craft
Metabolic dysfunction is a well-established feature of Alzheimer's disease (AD), evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D), hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29156129/small-molecule-mitochondrial-uncouplers-and-their-therapeutic-potential
#8
Elizabeth S Childress, Stephanie J Alexopoulos, Kyle L Hoehn, Webster L Santos
Small molecule mitohondrial uncouplers transport protons from the mitochondrial inner membrane space into the mitochondrial matrix independent of ATP synthase, uncoupling nutrient metabolism from ATP generation. The therapeutic potential of mitochondrial uncouplers have been investigated for the treatment metabolic diseases such as obesity and type 2 diabetes (T2D), as well as for neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. This perspective will review the mitochondrial uncouplers reported to date and explore their potential as therapeutics...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29141990/rna-sequencing-of-drosophila-melanogaster-head-tissue-on-high-sugar-and-high-fat-diets
#9
Wayne Hemphill, Osvaldo Rivera, Matthew Talbert
Obesity has been shown to increase risk for cardiovascular disease and type-2 diabetes. In addition, it has been implicated in aggravation of neurological conditions such as Alzheimer's. In the model organism Drosophila melanogaster, a physiological state mimicking diet-induced obesity can be induced by subjecting fruit flies to a solid medium disproportionately higher in sugar than protein or that has been supplemented with a rich source of saturated fat. These flies can exhibit increased circulating glucose levels, increased triglyceride content, insulin-like peptide resistance, and behavior indicative of neurological decline...
November 15, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29139169/sex-differences-in-the-phagocytic-and-migratory-activity-of-microglia-and-their-impairment-by-palmitic-acid
#10
Natalia Yanguas-Casás, Andrea Crespo-Castrillo, Maria L de Ceballos, Julie A Chowen, Iñigo Azcoitia, Maria Angeles Arevalo, Luis M Garcia-Segura
Sex differences in the incidence, clinical manifestation, disease course, and prognosis of neurological diseases, such as autism spectrum disorders or Alzheimer's disease, have been reported. Obesity has been postulated as a risk factor for cognitive decline and Alzheimer's disease and, during pregnancy, increases the risk of autism spectrum disorders in the offspring. Obesity is associated with increased serum and brain levels of free fatty acids, such as palmitic acid, which activate microglial cells triggering a potent inflammatory cascade...
November 15, 2017: Glia
https://www.readbyqxmd.com/read/29107872/inflammation-and-gut-brain-axis-link-obesity-to-cognitive-dysfunction-plausible-pharmacological-interventions
#11
REVIEW
Maite Solas, Fermin I Milagro, María J Ramírez, J Alfredo Martínez
Obesity prevalence is increasing steadily throughout the world's population in most countries and in parallel the prevalence of metabolic disorders including cardiovascular diseases and type 2 diabetes is also rising, but less is reported about excessive adiposity relationship with poorer cognitive performance, cognitive decline and dementia. Some human clinical studies have evidenced that obesity is related to the risk of the development of mild cognitive impairment, in the form of short-term memory and executive function deficits, as well as dementia and Alzheimer's disease...
November 3, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29103043/examining-the-relationship-between-trace-lithium-in-drinking-water-and-the-rising-rates-of-age-adjusted-alzheimer-s-disease-mortality-in-texas
#12
Val Andrew Fajardo, Val Andrei Fajardo, Paul J LeBlanc, Rebecca E K MacPherson
BACKGROUND: Alzheimer's disease (AD) mortality rates have steadily increased over time. Lithium, the current gold standard treatment for bipolar disorder, can exert neuroprotective effects against AD. OBJECTIVE: We examined the relationship between trace levels of lithium in drinking water and changes in AD mortality across several Texas counties. METHODS: 6,180 water samples from public wells since 2007 were obtained and averaged for 234 of 254 Texas counties...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29081698/population-based-study-of-risk-polymorphisms-associated-with-vascular-disorders-and-dementia
#13
Óscar Teijido, Juan Carlos Carril, Ramón Cacabelos
INTRODUCTION: Cardiovascular and neurodegenerative disorders are among the major causes of mortality in the developed countries. Population studies evaluate the genetic risk, i.e. the probability of an individual carrying a specific disease-associated polymorphism. Identification of risk polymorphisms is essential for an accurate diagnosis or prognosis of a number of pathologies. AIMS: The aim of this study was to characterize the influence of risk polymorphisms associated with lipid metabolism, hypertension, thrombosis, and dementia, in a large population of Spanish individuals affected by a variety of brain and vascular disorders as well as metabolic syndrome...
October 2017: Current Genomics
https://www.readbyqxmd.com/read/29079741/combined-x-ray-crystallography-and-computational-modeling-approach-to-investigate-the-hsp90-c-terminal-peptide-binding-to-fkbp51
#14
Rajnish Kumar, Martin Moche, Bengt Winblad, Pavel F Pavlov
FK506 binding protein of 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) co-chaperone involved in the regulation of steroid hormone receptors activity. It is known for its role in various regulatory pathways implicated in mood and stress-related disorders, cancer, obesity, Alzheimer's disease and corticosteroid resistant asthma. It consists of two FKBP12 like active peptidyl prolyl isomerase (PPIase) domains (an active FK1 and inactive FK2 domain) and one tetratricopeptide repeat (TPR) domain that mediates interaction with Hsp90 via its C-terminal MEEVD peptide...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29075003/trends-in-gpcr-drug-discovery-new-agents-targets-and-indications
#15
REVIEW
Alexander S Hauser, Misty M Attwood, Mathias Rask-Andersen, Helgi B Schiöth, David E Gloriam
G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased...
October 27, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/29066899/sex-differences-in-obesity-and-cognitive-function-in-a-cognitively-normal-aging-chinese-han-population
#16
Wei Li, Qi Qiu, Lin Sun, Ling Yue, Tao Wang, Xia Li, Shifu Xiao
BACKGROUND: Sex differences in Alzheimer's disease and mild cognitive impairment have been well recognized. However, sex differences in cognitive function and obesity in cognitively normal aging Chinese Han population have not attracted much attention. OBJECTIVE: The aim of this study was to investigate the relationship between sex, obesity, and cognitive function in an elderly Chinese population with normal cognitive function. SUBJECTS AND METHODS: A total of 228 cognitively normal aging participants (males/females =93/135) entered this study...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29038028/adiponectin-and-sporadic-alzheimer-s-disease-clinical-and-molecular-links
#17
REVIEW
Liliana Letra, Tiago Rodrigues, Paulo Matafome, Isabel Santana, Raquel Seiça
Obesity has been consistently associated with Alzheimer's disease (AD) though the exact mechanisms by which it influences cognition are still elusive and subject of current research. Adiponectin, the most abundant adipokine in circulation, is inversely correlated with adipose tissue dysfunction and seems to be a central player in this association. In fact, different signalling pathways are shared by adiponectin and proteins involved in AD pathophysiology and considerable amount of evidence supports its direct and indirect influence on β-amyloid and tau aggregates formation...
October 13, 2017: Frontiers in Neuroendocrinology
https://www.readbyqxmd.com/read/29024348/obesity-as-a-risk-factor-for-alzheimer-s-disease-weighing-the-evidence
#18
REVIEW
S Alford, D Patel, N Perakakis, C S Mantzoros
Alzheimer's disease (AD) is the sixth leading cause of death in the USA today; therefore, it is imperative that public health initiatives and clinical strategies are developed to prevent and effectively treat AD. Despite the enormous impact that AD has on individuals, families, society, and the health care system, there are no biomarkers to clearly identify those at risk for AD, public health prevention strategies in place, or treatments to address the underlying pathology or stop the progression of AD. There is ample scientific as well as empirical evidence that obesity and its metabolic and vascular comorbidities are related to AD and likely in the causative pathway...
October 10, 2017: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29016862/ube3a-deficiency-inhibits-amyloid-plaque-formation-in-appswe-ps1%C3%AE-e9-mouse-model-of-alzheimer-s-disease
#19
Brijesh Kumar Singh, Naman Vatsa, Vipendra Kumar, Shashi Shekhar, Ankit Sharma, Nihar Ranjan Jana
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in memory and cognitive function. Pathological hallmark of AD includes aberrant aggregation of amyloid beta (Aβ) peptide, which is produced upon sequential cleavage of amyloid precursor protein (APP) by β- and γ -secretases. On the contrary, α-secretase cleaves APP within the Aβ sequence and thereby prevents Aβ generation. Here, we investigated the role of ubiquitin ligase Ube3a (involved in synaptic function and plasticity) in the pathogenesis of AD using APPswe/PS1δE9 transgenic mouse model and first noticed that soluble pool of Ube3a was age-dependently decreased in AD mouse in comparison with wild type controls...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28994619/biological-evaluation-of-benzosuberones
#20
Haider Behbehani, Kamal M Dawood, Thoraya A Farghaly
Several natural products containing benzosuberone moiety are clinically reported as anti-tumor agents. Furthermore, several synthetic benzosuberones cited in this review exhibited wide range of theraputic activities such as bacteriostatic, anti-inflammatory, antidepressants and anti-tumor activities. Our recent review provides an overview of the different methods to synthesize the benzosuberones and their extensive biological activities. Areas covered: Thirty-two patents among 130 references are cited in this review that covered the recent inhibitory activities of the benzosuberone scaffolds and their broad area of biological applications up to the first quarter of 2017...
October 10, 2017: Expert Opinion on Therapeutic Patents
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