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https://www.readbyqxmd.com/read/29156377/establishment-of-induced-pluripotent-stem-cell-line-zzui010-a-from-an-alzheimer-s-disease-patient-carrying-an-app-gene-mutation
#1
Zhilei Wang, Pei Zhang, Yanlin Wang, Changhe Shi, Na Jing, Huifang Sun, Jing Yang, Yutao Liu, Xuejun Wen, Jin Zhang, Shoutao Zhang, Yuming Xu
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Previous studies have identified mutations in several genes, such as amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), in patients with early-onset (<65years) familial AD. Recently, a patient with an APP gene mutation was identified; the dermal fibroblasts of the patient were obtained and a line of induced pluripotent stem cells (iPSCs) was successfully generated using the Sendai-virus (SeV) delivery system...
November 3, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29155947/dementia-after-moderate-severe-traumatic-brain-injury-coexistence-of-multiple-proteinopathies
#2
Kimbra Kenney, Diego Iacono, Brian L Edlow, Douglas I Katz, Ramon Diaz-Arrastia, Kristen Dams-O'Connor, Daniel H Daneshvar, Allison Stevens, Allison L Moreau, Lee S Tirrell, Ani Varjabedian, Anastasia Yendiki, Andre van der Kouwe, Azma Mareyam, Jennifer A McNab, Wayne A Gordon, Bruce Fischl, Ann C McKee, Daniel P Perl
We report the clinical, neuroimaging, and neuropathologic characteristics of 2 patients who developed early onset dementia after a moderate-severe traumatic brain injury (TBI). Neuropathological evaluation revealed abundant β-amyloid neuritic and cored plaques, diffuse β-amyloid plaques, and frequent hyperphosphorylated-tau neurofibrillary tangles (NFT) involving much of the cortex, including insula and mammillary bodies in both cases. Case 1 additionally showed NFTs in both the superficial and deep cortical layers, occasional perivascular and depth-of-sulci NFTs, and parietal white matter rarefaction, which corresponded with decreased parietal fiber tracts observed on ex vivo MRI...
November 16, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29155708/enrichment-of-detergent-insoluble-protein-aggregates-from-human-postmortem-brain
#3
Ian Diner, Tram Nguyen, Nicholas T Seyfried
In this study, we describe an abbreviated single-step fractionation protocol for the enrichment of detergent-insoluble protein aggregates from human postmortem brain. The ionic detergent N-lauryl-sarcosine (sarkosyl) effectively solubilizes natively folded proteins in brain tissue allowing the enrichment of detergent-insoluble protein aggregates from a wide range of neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis, and prion diseases...
October 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155576/chronic-arsenic-exposure-increases-a%C3%AE-1-42-production-and-rage-expression-in-rat-brain
#4
Sandra Aurora Niño, Guadalupe Martel-Gallegos, Adriana Castro-Zavala, Benita Ortega-Berlanga, Juan Manuel Delgado, Hector Hernandez-Mendoza, E Romero-Guzman, Judith Rios-Lugo, Sergio Rosales-Mendoza, María Esther Jiménez-Capdeville, Sergio Zarazua
Chronic arsenic exposure during development is associated with alterations of chemical transmission and demyelination, which result in cognitive deficits and peripheral neuropathies. At cellular level, arsenic toxicity involves increased generation of reactive species that induce severe cellular alterations such as DNA fragmentation, apoptosis and lipid peroxidation. It has been proposed that arsenic-associated neurodegeneration could evolve to Alzheimer disease in later life.1,2 In this study, the effects of chronic exposure to inorganic arsenic (3 ppm by drinking water) in Wistar rats on the production and elimination of Amyloid-β (Aβ) were evaluated...
November 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29154269/early-and-persistent-o-glcnac-protein-modification-in-the-streptozotocin-model-of%C3%A2-alzheimer-s-disease
#5
João Paulo Almeida Dos Santos, Adriana Vizuete, Fernanda Hansen, Regina Biasibetti, Carlos-Alberto Gonçalves
 O-GlcNAc transferase (OGT), an enzyme highly expressed in brain tissue, catalyzes the addition of N-acetyl-glucosamine (GlcNAc) to hydroxyl residues of serine and threonine of proteins. Brain protein O-GlcNAcylation is diminished in Alzheimer's disease (AD), and OGT targets include proteins of the insulin-signaling pathway (e.g., insulin receptor susbtrate-1, IRS-1). We hypothesized that ICV streptozotocin (STZ) also affects O-GlcNAc protein modification. We investigated hippocampal metabolic changes in Wistar rats, particularly OGT levels and insulin resistance, as well as related astroglial activities, immediately after ICV STZ administration (first week) and later on (fourth week)...
November 16, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29153990/cell-type-dependent-alzheimer-s-disease-phenotypes-probing-the-biology-of%C3%A2-selective-neuronal-vulnerability
#6
Christina R Muratore, Constance Zhou, Meichen Liao, Marty A Fernandez, Walter M Taylor, Valentina N Lagomarsino, Richard V Pearse, Heather C Rice, Joseph M Negri, Amy He, Priya Srikanth, Dana G Callahan, Taehwan Shin, Monica Zhou, David A Bennett, Scott Noggle, J Christopher Love, Dennis J Selkoe, Tracy L Young-Pearse
Alzheimer's disease (AD) induces memory and cognitive impairment in the absence of motor and sensory deficits during its early and middle course. A major unresolved question is the basis for this selective neuronal vulnerability. Aβ, which plays a central role in AD pathogenesis, is generated throughout the brain, yet some regions outside of the limbic and cerebral cortices are relatively spared from Aβ plaque deposition and synapse loss. Here, we examine neurons derived from iPSCs of patients harboring an amyloid precursor protein mutation to quantify AD-relevant phenotypes following directed differentiation to rostral fates of the brain (vulnerable) and caudal fates (relatively spared) in AD...
November 13, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29150540/increased-florbetapir-binding-in-the-temporal-neocortex-from-age-20-to-60-years
#7
Julie Gonneaud, Eider M Arenaza-Urquijo, Florence Mézenge, Brigitte Landeau, Malo Gaubert, Alexandre Bejanin, Robin de Flores, Miranka Wirth, Clémence Tomadesso, Géraldine Poisnel, Ahmed Abbas, Béatrice Desgranges, Gaël Chételat
OBJECTIVE: To improve our understanding of early β-amyloid (Aβ) accumulation processes using florbetapir-PET scan in 20- to 60-year-old individuals. METHODS: Seventy-six cognitively normal individuals aged 20 to 60 years, 57 cognitively normal older individuals (61-84 years old), and 70 patients with mild cognitive impairment or probable Alzheimer disease (AD) underwent a florbetapir-PET scan. Images were spatially normalized and scaled using the whole cerebellum...
November 17, 2017: Neurology
https://www.readbyqxmd.com/read/29149791/the-dementia-care-coordination-program-engaging-health-systems-in-caregiver-supports
#8
Pamela Nadash, Nina M Silverstein, Frank Porell
This paper reports on a process evaluation using mixed methods to assess a Dementia Care Coordination Program, which is distinctive in using the medical system, rather than direct outreach, to identify and refer families to supports provided by an Alzheimer's Association chapter via dedicated care consultants. One care consultant received referrals from individual physicians, while the other, employed by a health plan, received referrals from health plan case managers. Through key informant interviews, focus groups, and physician and caregiver surveys, we identified key issues, finding high rates of stakeholder satisfaction, but some practical issues around information sharing and data tracking...
January 1, 2017: Dementia
https://www.readbyqxmd.com/read/29146049/common-and-rare-tbk1-variants-in-early-onset-alzheimer-disease-in-a-european-cohort
#9
Jan Verheijen, Julie van der Zee, Ilse Gijselinck, Tobi Van den Bossche, Lubina Dillen, Bavo Heeman, Estrella Gómez-Tortosa, Albert Lladó, Raquel Sanchez-Valle, Caroline Graff, Pau Pastor, Maria A Pastor, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Jordi Clarimon, Alexandre de Mendonça, Ellen Gelpi, Magda Tsolaki, Janine Diehl-Schmid, Benedetta Nacmias, Maria Rosário Almeida, Barbara Borroni, Radoslav Matej, Agustín Ruiz, Sebastiaan Engelborghs, Rik Vandenberghe, Peter P De Deyn, Marc Cruts, Christine Van Broeckhoven, Kristel Sleegers
TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls...
October 25, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29141977/vitamins-associated-with-brain-aging-mild-cognitive-impairment-and-alzheimer-disease-biomarkers-epidemiological-and-experimental-evidence-plausible-mechanisms-and-knowledge-gaps
#10
REVIEW
Michael Fenech
The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141953/amyloid-%C3%AE-42-peptide-is-toxic-to-non-neural-cells-in-drosophila-yielding-a-characteristic-metabolite-profile-and-the-effect-can-be-suppressed-by-pi3k
#11
Mercedes Arnés, Sergio Casas-Tintó, Anders Malmendal, Alberto Ferrús
The human Aβ42 peptide is associated with Alzheimer's disease through its deleterious effects in neurons. Expressing the human peptide in adult Drosophila in a tissue- and time-controlled manner, we show that Aβ42 is also toxic in non-neural cells, neurosecretory and epithelial cell types in particular. This form of toxicity includes the aberrant signaling by Wingless morphogen leading to the eventual activation of Caspase 3. Preventing Caspase 3 activation by means of p53 keeps epithelial cells from elimination but maintains the Aβ42 toxicity yielding more severe deleterious effects to the organism...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29141449/decisions-and-attitudes-regarding-participation-and-proxy-in-clinical-trials-among-patients-with-impaired-cognitive-function
#12
S Stormoen, I M Tallberg, O Almkvist, M Eriksdotter, E Sundström
Background Medical decision-making capacity is impaired in Alzheimer's disease and mild cognitive impairment. Medical decision-making capacity depends on many different cognitive functions and varies due to situation and cognitive, social, and emotional status of the patient. Our aim was to analyze dementia patients' capacity to estimate risks and benefits in different clinical trials and determine how cognitive decline affects their attitude toward possible participation and proxy consent. Methods Groups: Alzheimer's disease (n = 20), mild cognitive impairment (n = 21) and healthy controls (n = 33)...
January 1, 2017: Dementia
https://www.readbyqxmd.com/read/29141366/-in-vitro-early-detection-of-amyloid-plaques-in-alzheimer-s-disease-by-pittsburgh-compound-b-modified-magnetic-nanoparticles
#13
J Q Zeng, J Q Wu, M H Li, P J Wang
Objective: To construct magnetic nanoparticles targeting β-amyloid (Aβ) plaques, the pathological biomarker of Alzheimer's disease (AD) and to study their binding capability in vitro. Methods: Superparamagnetic nanoparticles Mn(0.6)Zn(0.4)Fe(2)O(4) (MZF) were coated with amphiphilic star-block copolymeric micelles and modified with Aβ-specific probe Pittsburgh compound B (PiB) to construct a novel magnetic nanoparticle MZF-PiB, which specifically targeted amyloid plaques. Transmission electron microscope was used to study the morphological features of MZF-PiB...
November 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29138762/identifying-cu-ii-amyloid-peptide-binding-intermediates-in-the-early-stages-of-aggregation-by-resonance-raman-spectroscopy-a-simulation-study
#14
Hao Ren, Yu Zhang, Sibei Guo, Na Lin, Li Deng, Tongtao Yue, Fang Huang
The aggregation of amyloid beta (Aβ) peptides plays a crucial role in the pathology and etiology of Alzheimer's disease. Experimental evidence shows that copper ion is an aggregation-prone species with the ability to coordinately bind to Aβ and further induce the formation of neurotoxic Aβ oligomers. However, the detailed structures of Cu(ii)-Aβ complexes have not been illustrated, and the kinetics and dynamics of the Cu(ii) binding are not well understood. Two Cu(ii)-Aβ complexes have been proposed to exist under physiological conditions, and another two might exist at higher pH values...
November 15, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29137651/abnormal-dendritic-calcium-activity-and-synaptic-depotentiation-occur-early-in-a-mouse-model-of-alzheimer-s-disease
#15
Yang Bai, Miao Li, Yanmei Zhou, Lei Ma, Qian Qiao, Wanling Hu, Wei Li, Zachary Patrick Wills, Wen-Biao Gan
BACKGROUND: Alzheimer's disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. METHODS: We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice...
November 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29137441/aberrations-in-circulating-inflammatory-cytokine-levels-in-patients-with-down-syndrome-a-meta-analysis
#16
Yan Zhang, Meng Che, Jing Yuan, Yun Yu, Chang Cao, Xiao-Yan Qin, Yong Cheng
Evidence suggests that immune system alterations in Down syndrome (DS) may be early events that drive neuropathological and cognitive changes of Alzheimer's disease. The primary objective of this meta-analysis was to investigate whether there is an abnormal cytokine profile in DS patients when compared with healthy control (HC) subjects. A systematic search of Pubmed and Web of Science identified 19 studies with 957 DS patients and 541 HC subjects for this meta-analysis. Random effects meta-analysis demonstrated that patients with DS had significantly increased circulating tumor necrosis factor-α (Hedges' g = 1...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136123/amyloid-network-topology-characterizes-the-progression-of-alzheimer-s-disease-during-the-predementia-stages
#17
Joana B Pereira, Tor Olof Strandberg, Sebastian Palmqvist, Giovanni Volpe, Danielle van Westen, Eric Westman, Oskar Hansson
There is increasing evidence showing that the accumulation of the amyloid-β (Aβ) peptide into extracellular plaques is a central event in Alzheimer's disease (AD). These abnormalities can be detected as lowered levels of Aβ42 in the cerebrospinal fluid (CSF) and are followed by increased amyloid burden on positron emission tomography (PET) several years before the onset of dementia. The aim of this study was to assess amyloid network topology in nondemented individuals with early stage Aβ accumulation, defined as abnormal CSF Aβ42 levels and normal Florbetapir PET (CSF+/PET-), and more advanced Aβ accumulation, defined as both abnormal CSF Aβ42 and Florbetapir PET (CSF+/PET+)...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29134771/detection-of-%C3%AE-amyloid-by-sialic-acid-coated-bovine-serum-albumin-magnetic-nanoparticles-in-a-mouse-model-of-alzheimer-s-disease
#18
Seyedmehdi Hossaini Nasr, Hovig Kouyoumdjian, Christiane Mallett, Sherif Ramadan, David C Zhu, Erik M Shapiro, Xuefei Huang
The accumulation and formation of β-amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP-BSAx -Sia) to overcome the challenges in Aβ imaging in vivo...
November 14, 2017: Small
https://www.readbyqxmd.com/read/29134465/current-role-for-biomarkers-in-clinical-diagnosis-of-alzheimer-disease-and-frontotemporal-dementia
#19
REVIEW
Nasim Sheikh-Bahaei, Seyed Ahmad Sajjadi, Aimee L Pierce
Purpose of review Alzheimer's disease (AD) and frontotemporal dementia can often be diagnosed accurately with careful clinical history, cognitive testing, neurological examination, and structural brain MRI. However, there are certain circumstances wherein detection of specific biomarkers of neurodegeneration or underlying AD pathology will impact the clinical diagnosis or treatment plan. We will review the currently available biomarkers for AD and frontotemporal dementia (FTD) and discuss their clinical importance...
November 14, 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29134122/platelet-phosphorylated-tdp-43-an-exploratory-study-for-a-peripheral-surrogate-biomarker-development-for-alzheimer-s-disease
#20
Rodger Wilhite, Jessica M Sage, Abdurrahman Bouzid, Tyler Primavera, Abdulbaki Agbas
Aim: Alzheimer's disease (AD) and other forms of dementia create a noncurable disease population in world's societies. To develop a blood-based biomarker is important so that the remedial or disease-altering therapeutic intervention for AD patients would be available at the early stage. Materials & methods: TDP-43 levels were analyzed in postmortem brain tissue and platelets of AD and control subjects. Results: We observed an increased TDP-43 (<60%) in postmortem AD brain regions and similar trends were also observed in patient's platelets...
November 2017: Future Science OA
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