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https://www.readbyqxmd.com/read/28812113/-pathophysiology-of-intracranial-injuries
#1
REVIEW
D Lahner, G Fritsch
Traumatic brain injury (TBI) constitutes a heterogeneous condition that affects the most complex organ of the human body. It is commonly classified by its location as focal injury (e.g. epidural hematoma) and diffuse injury (e.g. diffuse axonal shearing injury) as well as by primary and secondary tissue injury. Accordingly, direct mechanical force causes the primary insult. The tissue damage occurring afterwards is subsumed under the term secondary brain damage. Some of these processes are overlapping and include in the early phase local cerebral ischemia resulting in excitotoxicity, which together with the triggered neuroinflammatory cascade causes the formation of cerebral edema and ultimately increased intracranial pressure once the intracranial compliance is exhausted...
August 15, 2017: Der Unfallchirurg
https://www.readbyqxmd.com/read/28811268/antecedent-adhd-dementia-and-metabolic-dysregulation-a-u-s-based-cohort-analysis
#2
Keith Fluegge, Kyle Fluegge
INTRODUCTION: Epidemiological and genetic studies have reported a link between antecedent ADHD and dementia. The underpinning mechanisms of these associations are not known and have generated considerable speculation. METHODS: We have extracted hospitalization discharge data on dementia and ADHD (representing a severe phenotype) from the Healthcare Cost and Utilization Project (HCUPnet) and utilized a Poisson regression with two-ways fixed effects to investigate this association...
August 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28811267/app-a%C3%AE-structural-diversity-and-alzheimer-s-disease-pathogenesis
#3
REVIEW
Alex E Roher, Tyler A Kokjohn, Steven G Clarke, Michael R Sierks, Chera L Maarouf, Geidy E Serrano, Marwan S Sabbagh, Thomas G Beach
The amyloid cascade hypothesis of Alzheimer's disease (AD) proposes amyloid- β (Aβ) is a chief pathological element of dementia. AD therapies have targeted monomeric and oligomeric Aβ 1-40 and 1-42 peptides. However, alternative APP proteolytic processing produces a complex roster of Aβ species. In addition, Aβ peptides are subject to extensive posttranslational modification (PTM). We propose that amplified production of some APP/Aβ species, perhaps exacerbated by differential gene expression and reduced peptide degradation, creates a diverse spectrum of modified species which disrupt brain homeostasis and accelerate AD neurodegeneration...
August 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28810189/hydroxy-substituted-trans-cinnamoyl-derivatives-as-multifunctional-tools-in-the-context-of-alzheimer-s-disease
#4
Angela De Simone, Manuela Bartolini, Andrea Baschieri, Kim Y P Apperley, Huan Huan Chen, Melissa Guardigni, Serena Montanari, Tereza Kobrlova, Ondrej Soukup, Luca Valgimigli, Vincenza Andrisano, Jeffrey W Keillor, Manuela Basso, Andrea Milelli
Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments...
July 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28809651/effectiveness-of-occupational-therapy-interventions-to-enhance-occupational-performance-for-adults-with-alzheimer-s-disease-and-related-major-neurocognitive-disorders-a-systematic-review
#5
Stacy Smallfield, Cindy Heckenlaible
OBJECTIVE: The purpose of this systematic review was to describe the evidence for the effectiveness of interventions designed to establish, modify, and maintain occupations for adults with Alzheimer's disease (AD) and related neurocognitive disorders. METHOD: Titles and abstracts of 2,597 articles were reviewed, of which 256 were retrieved for full review and 52 met inclusion criteria. U.S. Preventive Services Task Force levels of certainty and grade definitions were used to describe the strength of evidence...
September 2017: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
https://www.readbyqxmd.com/read/28809040/a-mobile-app-for-sharing-contacts-on-your-cell-an-editorial-highlight-for-the-physiological-role-of-the-amyloid-precursor-protein-app-as-an-adhesion-molecule-in-the-developing-nervous-system-on-doi-10-1111-jnc-14122
#6
EDITORIAL
George William Rebeck, Daniel T S Pak
This is an Editorial for a review that Sosa and coworkers present in the current issue of the Journal of Neurochemistry of physiological functions for amyloid precursor protein (APP) at dynamic cellular contact sites such as growth cones, neuronal migration tracts, and synapses. Here, APP physically links the extracellular and intracellular milieus through a multitude of binding partners. From these observations, the authors offer a model of APP as a cell adhesion molecule in the brain, providing a context for understanding its role in Alzheimer's disease and Down syndrome...
August 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28808138/an-ampk-dependent-regulatory-pathway-in-tau-mediated-toxicity
#7
Alessia Galasso, Charles S Cameron, Bruno G Frenguelli, Kevin G Moffat
Neurodegenerative tauopathies are characterized by accumulation of hyperphosphorylated tau aggregates primarily degraded by autophagy.The 5'AMP-activated protein kinase (AMPK) is expressed in most cells, including neurons. Alongside its metabolic functions, it is also known to be activated in Alzheimer's brains, phosphorylate tau and be a critical autophagy activator. Whether it plays a neurotoxic or neuroprotective role remains unclear. Complexly in tauopathies, while stress conditions can result in AMPK activation enhancing tau-mediated toxicity, AMPK activation is not always concomitant with autophagic induction...
August 14, 2017: Biology Open
https://www.readbyqxmd.com/read/28805765/-systemic-inflammatory-markers-in-age-associated-cognitive-impairment-and-alzheimer-s-disease
#8
T P Kliushnik, L V Androsova, N M Mikhaylova, I V Kolykhalov, S A Zozulya, A M Dupin
AIM: To determine a complex of immune markers reflecting various links of multicomponent inflammatory reactions in amnestic type of mild cognitive impairment (aMCI) in comparison with Alzheimer's disease (AD). MATERIAL AND METHODS: Sixty-seven patients with aMCI, aged 72 [63; 77] years, and 91 patients with Alzheimer's disease at the age of 74 [68; 79] years were examined. The aMCI was diagnosed according to the criteria of R.S. Petersen et al. (1999) and B. Dubois et al...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28805100/older-adults-with-a-combination-of-vision-and-hearing-impairment-experience-higher-rates-of-cognitive-impairment-functional-dependence-and-worse-outcomes-across-a-set-of-quality-indicators
#9
Jacob G S Davidson, Dawn M Guthrie
OBJECTIVES: Hearing and vision impairment were examined across several health-related outcomes and across a set of quality indicators (QIs) in home care clients with both vision and hearing loss (or dual sensory impairment [DSI]). METHOD: Data collected using the Resident Assessment Instrument for Home Care (RAI-HC) were analyzed in a sample of older home care clients. The QIs represent the proportion of clients experiencing negative outcomes (e.g., falls, social isolation)...
August 1, 2017: Journal of Aging and Health
https://www.readbyqxmd.com/read/28804509/lifetime-stress-exposure-and-health-a-review-of-contemporary-assessment-methods-and-biological-mechanisms
#10
Grant S Shields, George M Slavich
Life stress is a central construct in health research because it is associated with increased risk for a variety of serious mental and physical health problems, including anxiety disorders, depression, cardiovascular disease, autoimmune disorders, Alzheimer's disease, certain cancers, and other diseases of aging. In this review, we examine how lifetime stress exposure contributes to elevated disease risk, and explore ongoing measurement and scientific issues related to this topic. To accomplish these goals, we first review existing instruments that have been developed for assessing perceived stress, self-reported life events, interviewer-assessed life stressors, and lifetime stress exposure...
August 2017: Social and Personality Psychology Compass
https://www.readbyqxmd.com/read/28803148/combustion-derived-nanoparticles-the-neuroenteric-system-cervical-vagus-hyperphosphorylated-alpha-synuclein-and-tau-in-young-mexico-city-residents
#11
Lilian Calderón-Garcidueñas, Rafael Reynoso-Robles, Beatriz Pérez-Guillé, Partha S Mukherjee, Angélica Gónzalez-Maciel
Mexico City (MC) young residents are exposed to high levels of fine particulate matter (PM2.5), have high frontal concentrations of combustion-derived nanoparticles (CDNPs), accumulation of hyperphosphorylated aggregated α-synuclein (α-Syn) and early Parkinson's disease (PD). Swallowed CDNPs have easy access to epithelium and submucosa, damaging gastrointestinal (GI) barrier integrity and accessing the enteric nervous system (ENS). This study is focused on the ENS, vagus nerves and GI barrier in young MC v clean air controls...
August 9, 2017: Environmental Research
https://www.readbyqxmd.com/read/28800329/chronic-verubecestat-treatment-suppresses-amyloid-accumulation-in-advanced-aged-tg2576-a%C3%AE-ppswe-mice-without-inducing-microhemorrhage
#12
Stephanie Villarreal, Fuqiang Zhao, Lynn A Hyde, Daniel Holder, Thomas Forest, Marie Sondey, Xia Chen, Cyrille Sur, Eric M Parker, Matthew E Kennedy
Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal Alzheimer's disease. Multiple anti-amyloid immunotherapies have been dose-limited by adverse amyloid related imaging abnormalities such as vasogenic edema (ARIA-E) and microhemorrhage (ARIA-H) observed in human trials and mice. Verubecestat was tested in a 12-week nonclinical study for the potential to exacerbate microhemorrhage (ARIA-H) profiles in 18-22-month-old post-plaque Tg2576-AβPPswe mice...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28799488/environment-and-neurodegenerative-diseases-an-update-on-mirna-role
#13
Margherita Ferrante, Gea Oliveri Conti
INTRODUCTION: The importance of neurodegenerative diseases on the management of public health is growing and the real role of the environment and miRNA in their occurrence is still unclear. miRNA can affect significantly the regulatory network. The complex variety and gene-regulatory capacity of miRNAs is particularly valuable in the brain, being a very complex organ with a functional specialization of neurons highly adaptable to environmental stimuli. In particular a miRNAs role is demonstrated in neurological diseases as the effect to toxic and mutagenic substances exposure by the environment...
August 11, 2017: MicroRNA
https://www.readbyqxmd.com/read/28799085/dimerization-leads-to-changes-in-app-amyloid-precursor-protein-trafficking-mediated-by-lrp1-and-sorla
#14
Simone Eggert, A C Gonzalez, C Thomas, S Schilling, S M Schwarz, C Tischer, V Adam, P Strecker, V Schmidt, T E Willnow, G Hermey, C U Pietrzik, E H Koo, Stefan Kins
Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization...
August 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28798225/ethical-issues-in-alzheimer-s-disease-research-involving-human-subjects
#15
Dena S Davis
As we aggressively pursue research to cure and prevent Alzheimer's disease, we encounter important ethical challenges. None of these challenges, if handled thoughtfully, would pose insurmountable barriers to research. But if they are ignored, they could slow the research process, alienate potential study subjects and do damage to research recruits and others. These challenges are (1) the necessity of very large cohorts of research subjects, recruited for lengthy studies, probably ending only in the subjects' death; (2) the creation of cohorts of 'study ready' volunteers, many of whom will be competent to consent at the beginning of the process, but move into cognitive impairment later; (3) reliance on adaptive trial design, creating challenges for informed consent, equipoise and justice; (4) the use of biomarkers and predictive tests that describe risk rather than certainty, and that can threaten participants' welfare if the information is obtained by insurance companies or long-term care providers; (5) the use of study partners that creates unique risks of harm to the relationship of subject and study partner...
August 10, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28797738/tissue-magnetic-susceptibility-mapping-as-a-marker-of-tau-pathology-in-alzheimer-s-disease
#16
J O'Callaghan, H Holmes, N Powell, J A Wells, O Ismail, I F Harrison, B Siow, R Johnson, Z Ahmed, A Fisher, S Meftah, M J O'Neill, T K Murray, E C Collins, K Shmueli, M F Lythgoe
Alzheimer's disease is connected to a number of other neurodegenerative conditions, known collectively as 'tauopathies', by the presence of aggregated tau protein in the brain. Neuroinflammation and oxidative stress in AD are associated with tau pathology and both the breakdown of axonal sheaths in white matter tracts and excess iron accumulation grey matter brain regions. Despite the identification of myelin and iron concentration as major sources of contrast in quantitative susceptibility maps of the brain, the sensitivity of this technique to tau pathology has yet to be explored...
August 4, 2017: NeuroImage
https://www.readbyqxmd.com/read/28797057/a%C3%AE-42-mediated-proteasome-inhibition-and-associated-tau-pathology-in-hippocampus-are-governed-by-a-lysosomal-response-involving-cathepsin-b-evidence-for-protective-crosstalk-between-protein-clearance-pathways
#17
Karen L G Farizatto, Uzoma S Ikonne, Michael F Almeida, Merari F R Ferrari, Ben A Bahr
Impaired protein clearance likely increases the risk of protein accumulation disorders including Alzheimer's disease (AD). Protein degradation through the proteasome pathway decreases with age and in AD brains, and the Aβ42 peptide has been shown to impair proteasome function in cultured cells and in a cell-free model. Here, Aβ42 was studied in brain tissue to measure changes in protein clearance pathways and related secondary pathology. Oligomerized Aβ42 (0.5-1.5 μM) reduced proteasome activity by 62% in hippocampal slice cultures over a 4-6-day period, corresponding with increased tau phosphorylation and reduced synaptophysin levels...
2017: PloS One
https://www.readbyqxmd.com/read/28795133/performance-of-18-f-flutemetamol-amyloid-imaging-against-the-neuritic-plaque-component-of-cerad-and-the-current-2012-nia-aa-recommendations-for-the-neuropathologic-diagnosis-of-alzheimer-s-disease
#18
Stephen Salloway, Jose E Gamez, Upinder Singh, Carl H Sadowsky, Teresa Villena, Marwan N Sabbagh, Thomas G Beach, Ranjan Duara, Adam S Fleisher, Kirk A Frey, Zuzana Walker, Arvinder Hunjan, Yavir M Escovar, Marc E Agronin, Joel Ross, Andrea Bozoki, Mary Akinola, Jiong Shi, Rik Vandenberghe, Milos D Ikonomovic, Paul F Sherwin, Gill Farrar, Adrian P L Smith, Christopher J Buckley, Dietmar Rudolf Thal, Michelle Zanette, Craig Curtis
INTRODUCTION: Performance of the amyloid tracer [(18)F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD "original" and "modified" and the amyloid component of the 2012 NIA-AA guidelines). METHODS: After [(18)F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28794819/upregulation-of-autophagy-genes-and-the-unfolded-protein-response-in-human-heart-failure
#19
Brian C Jensen, Scott J Bultman, Darcy Holley, Wei Tang, Gustaaf de Ridder, Salvatore Pizzo, Dawn Bowles, Monte S Willis
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be profound and result in a process termed "proteotoxicity". While proteotoxicity is best known for its role in mediating the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, its role in human heart failure also has been recognized. The UPR involves three branches, including PERK, ATF6, and IRE1...
2017: International Journal of Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28794261/neuroprotective-astrocyte-derived-insulin-igf-1-stimulate-endocytic-processing-and-extracellular-release-of-neuron-bound-a%C3%AE-oligomers
#20
Jason Pitt, Kyle C Wilcox, Vanessa Tortelli, Luan Pereira Diniz, Maira S Oliveira, Cassandra Dobbins, Xiao-Wen Yu, Sathwik Nandamuri, Flávia C A Gomes, Nadia DiNunno, Kirsten L Viola, Fernanda G De Felice, Sergio T Ferreira, William L Klein
Synaptopathy underlying memory deficits in Alzheimer's disease (AD) is increasingly thought to be instigated by toxic oligomers of the amyloid beta peptide (AβOs). Given the long latency and incomplete penetrance of AD dementia with respect to Aβ pathology, we hypothesized that factors present in the CNS may physiologically protect neurons from the deleterious impact of AβOs. Here we employed physically-separated neuron-astrocyte co-cultures to investigate potential non cell-autonomous neuroprotective factors influencing AβO toxicity...
August 9, 2017: Molecular Biology of the Cell
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