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Alzheimer's etiologies

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https://www.readbyqxmd.com/read/28930654/a-tale-of-two-genes-microglial-apoe-and-trem2
#1
Anna A Pimenova, Edoardo Marcora, Alison M Goate
Microglial cell function is implicated in the etiology of Alzheimer's disease by human genetics. In this issue of Immunity, Krasemann et al. (2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis that might be amenable to therapeutic targeting.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28924872/-alzheimer-s-disease-from-auguste-deter-to-the-present-progress-disappointments-and-open-questions
#2
REVIEW
Johannes Pantel
AIM: The present article aims to provide a short overview of the discovery history, conceptual development, as well as on current neurobiological and pharmacological research questions in the field of Alzheimer's disease (AD). In view of the long hoped for but so far unachieved therapeutic breakthrough, this also includes a critical reflection of current research paradigms. MATERIAL AND METHODS: Starting from the first case report described by Alois Alzheimer in 1906, the historical impact of his seminal discovery is reconstructed...
September 18, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28904096/ripk1-mediates-a-disease-associated-microglial-response-in-alzheimer-s-disease
#3
Dimitry Ofengeim, Sonia Mazzitelli, Yasushi Ito, Judy Park DeWitt, Lauren Mifflin, Chengyu Zou, Sudeshna Das, Xian Adiconis, Hongbo Chen, Hong Zhu, Michelle A Kelliher, Joshua Z Levin, Junying Yuan
Dysfunction of microglia is known to play an important role in Alzheimer's disease (AD). Here, we investigated the role of RIPK1 in microglia mediating the pathogenesis of AD. RIPK1 is highly expressed by microglial cells in human AD brains. Using the amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model, we found that inhibition of RIPK1, using both pharmacological and genetic means, reduced amyloid burden, the levels of inflammatory cytokines, and memory deficits. Furthermore, inhibition of RIPK1 promoted microglial degradation of Aβ in vitro...
September 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28901441/profiling-of-differentially-expressed-genes-in-adipose-tissues-of-multiple-symmetric-lipomatosis
#4
Ke Chen, Linghao Wang, Wenjun Yang, Changfa Wang, Gui Hu, Zhaohui Mo
Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by aberrant multiple and symmetric subcutaneous adipose tissue accumulation in the face, neck, shoulders, back, chest and abdomen, severely affecting the quality of life of patients. At present, precise MSL etiology and pathogenesis remain to be elucidated. The present study first utilized a digital gene expression technique with a next‑generation sequencing platform to profile differentially expressed genes in three cases of MSL vs. normal control tissue...
September 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28890698/multi-target-screening-and-experimental-validation-of-natural-products-from-selaginella-plants-against-alzheimer-s-disease
#5
Yin-Hua Deng, Ning-Ning Wang, Zhen-Xing Zou, Lin Zhang, Kang-Ping Xu, Alex F Chen, Dong-Sheng Cao, Gui-Shan Tan
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder which is considered to be the most common cause of dementia. It has a greater impact not only on the learning and memory disturbances but also on social and economy. Currently, there are mainly single-target drugs for AD treatment but the complexity and multiple etiologies of AD make them difficult to obtain desirable therapeutic effects. Therefore, the choice of multi-target drugs will be a potential effective strategy inAD treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28887919/cassia-tora-linn-a-boon-to-alzheimer-s-disease-for-its-anti-amyloidogenic-and-cholinergic-activities
#6
K R Chethana, Fatma Sezer Senol, Ilkay Erdogan Orhan, K R Anilakumar, Rangappa S Keri
BACKGROUND: Drug discovery from natural products as alternatives for Alzheimer's disease (AD) is a current trend. For which plant is an alternative for searching potential molecule for treating AD. Availability of Cassia tora as weed and abundance in nature makes it as potential source. Many plants group under Leguminosae family has potential medicinal property of which Cassia tora is an appropriate choice, to know potency against AD. Etiology of AD is described by senile plaques and neurofibrillary tangles...
September 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28879407/microrna-profiling-in-aging-brain-of-psen1-psen2-double-knockout-mice
#7
Suji Ham, Tae Kyoo Kim, Sangjoon Lee, Ya-Ping Tang, Heh-In Im
MicroRNAs are small non-coding RNAs that function as regulators of gene expression. The altered expression of microRNAs influences the pathogenesis of Alzheimer's disease. Many researchers have focused on studies based on the relatively distinctive etiology of familial Alzheimer's disease due to the absence of risk factors in the pathogenesis of sporadic Alzheimer's disease. Although there is a limitation in Alzheimer's disease studies, both Alzheimer's disease types have a common risk factor-aging. No study to date has examined the aging factor in Alzheimer's disease animal models with microRNAs...
September 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28870582/linking-alzheimer-s-disease-and-type-2-diabetes-novel-shared-susceptibility-genes-detected-by-cfdr-approach
#8
Xia-Fang Wang, Xu Lin, Ding-You Li, Rou Zhou, Jonathan Greenbaum, Yuan-Cheng Chen, Chun-Ping Zeng, Lin-Ping Peng, Ke-Hao Wu, Zeng-Xin Ao, Jun-Min Lu, Yan-Fang Guo, Jie Shen, Hong-Wen Deng
BACKGROUND: Both type 2 diabetes (T2D) and Alzheimer's disease (AD) occur commonly in the aging populations and T2D has been considered as an important risk factor for AD. The heritability of both diseases is estimated to be over 50%. However, common pleiotropic single-nucleotide polymorphisms (SNPs)/loci have not been well-defined. The aim of this study is to analyze two large public accessible GWAS datasets to identify novel common genetic loci for T2D and/or AD. METHODS AND MATERIALS: The recently developed novel conditional false discovery rate (cFDR) approach was used to analyze the summary GWAS datasets from International Genomics of Alzheimer's Project (IGAP) and Diabetes Genetics Replication And Meta-analysis (DIAGRAM) to identify novel susceptibility genes for AD and T2D...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28869480/genetically-predicted-adult-height-an-alzheimer-s-disease
#9
Susanna C Larsson, Matthew Traylor, Stephen Burgess, Hugh S Markus
BACKGROUND: Observational studies have linked increased adult height with better cognitive performance and reduced risk of Alzheimer's disease (AD). It is unclear whether the associations are due to shared biological processes that influence height and AD or due to confounding by early life exposures or environmental factors. OBJECTIVE: To use a genetic approach to investigate the association between adult height and AD. METHODS: We selected 682 single nucleotide polymorphisms (SNPs) associated with height at genome-wide significance (p < 5×10-8) in the Genetic Investigation of ANthropometric Traits (GIANT) consortium...
August 30, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28869135/genetics-of-alzheimer-s-disease-from-pathogenesis-to-clinical-usage
#10
REVIEW
Wen Shao, Dantao Peng, Xiaomin Wang
Alzheimer's disease (AD) is the most common type of dementia and has caused a major global health concern. Understanding the etiology of AD can be beneficial for the diagnosis and intervention of this disease. Genetics plays a vital role in the pathogenesis of AD. Research methods in genetics such as the linkage analysis, study of candidate genes, genome-wide association study (GWAS), and next-generation sequencing (NGS) technology help us map the genetic information in AD, which can not only provide a new insight into the pathogenesis of AD but also be beneficial for early targeted intervention of AD...
August 28, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28867578/streptozotocin-induced-hippocampal-astrogliosis-and-insulin-signaling-malfunction-as-experimental-scales-for-subclinical-sporadic-alzheimer-model
#11
Farzaneh Rostami, Mohammad Javan, Ali Moghimi, Aliakbar Haddad-Mashadrizeh, Masoud Fereidoni
AIMS: Insulin signaling malfunction has recently been suggested as a preliminary event involved in the etiology of Sporadic Alzheimer's disease (SAD). In order to develop insulin resistance-related SAD model, rats were treated with streptozotocin, intracerebroventricularly (icv-STZ). Nevertheless, given the lack of knowledge regarding sub-clinical stages of SAD, the current challenging issue is establishing a practical pre-clinical SAD model. Despite some proposed mechanisms, such as insulin malfunction, neuroinflammation, and gliosis, icv-STZ mechanism of action is not fully understood yet and Streptozotocin-induced rat model of Alzheimer has still major shortcomings...
August 31, 2017: Life Sciences
https://www.readbyqxmd.com/read/28865022/drebrin-in-alzheimer-s-disease
#12
Yuta Ishizuka, Kenji Hanamura
Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by severe progressive memory and cognitive impairment. The brain of AD patients has an abundance of two abnormal structures, amyloid plaques (senile plaques) and neurofibrillary tangles. In addition, drebrin loss is another hallmark of AD brains, which is a common feature in the brain of both AD patients and AD mouse models. Strong evidence from human genetics and transgenic mouse models has indicated that amyloid β (Aβ) is part of the etiology and pathogenesis of AD...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28855981/role-of-bace1-in-alzheimer-s-synaptic-function
#13
REVIEW
Brati Das, Riqiang Yan
Alzheimer's disease (AD) is the most common age-dependent disease of dementia, and there is currently no cure available. This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles. Although the exact etiology of AD remains a mystery, studies over the past 30 have shown that abnormal generation or accumulation of β-amyloid peptides (Aβ) is likely to be a predominant early event in AD pathological development. Aβ is generated from amyloid precursor protein (APP) via proteolytic cleavage by β-site APP cleaving enzyme 1 (BACE1)...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28840063/p53-dysfunction-in-neurodegenerative-diseases-the-cause-or-effect-of-pathological-changes
#14
REVIEW
Aleksandra Szybińska, Wiesława Leśniak
Neurodegenerative diseases are a heterogeneous, mostly age-associated group of disorders characterized by progressive neuronal loss, the most prevalent being Alzheimer disease. It is anticipated that, with continuously increasing life expectancy, these diseases will pose a serious social and health problem in the near feature. Meanwhile, however, their etiology remains largely obscure even though all possible novel clues are being thoroughly examined. In this regard, a concept has been proposed that p53, as a transcription factor controlling many vital cellular pathways including apoptosis, may contribute to neuronal death common to all neurodegenerative disorders...
July 2017: Aging and Disease
https://www.readbyqxmd.com/read/28832675/time-course-global-proteome-analyses-reveal-an-inverse-correlation-between-a%C3%AE-burden-and-immunoglobulin-m-levels-in-the-appnl-f-mouse-model-of-alzheimer-disease
#15
Hansen Wang, Declan Williams, Jennifer Griffin, Takashi Saito, Takaomi C Saido, Paul E Fraser, Ekaterina Rogaeva, Gerold Schmitt-Ulms
Alzheimer disease (AD) stands out amongst highly prevalent diseases because there is no effective treatment nor can the disease be reliably diagnosed at an early stage. A hallmark of AD is the accumulation of aggregation-prone amyloid β peptides (Aβ), the main constituent of amyloid plaques. To identify Aβ-dependent changes to the global proteome we used the recently introduced APPNL-F mouse model of AD, which faithfully recapitulates the Aβ pathology of the disease, and a workflow that interrogated the brain proteome of these mice by quantitative mass spectrometry at three different ages...
2017: PloS One
https://www.readbyqxmd.com/read/28831921/in-silico-studies-in-drug-research-against-neurodegenerative-diseases
#16
Farahnaz Rezaei Makhouri, Jahan B Ghasemi
Neurodegenerative diseases such as Alzheimer's disease (AD), progressive neurodegenerative forms of Huntington's disease, Parkinson's disease (PD), amyotrophic lateral sclerosis, spinal cerebellar ataxias, and spinal and bulbar muscular atrophy are described by slow and selective dysfunction and degeneration of neurons and axons in the central nervous system (CNS). Computer-aided or in silico design methods have matured into powerful tools for reducing the number of ligands that should be screened in experimental assays...
August 22, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28830516/cost-of-diagnosing-dementia-in-a-german-memory-clinic
#17
Bernhard Michalowsky, Steffen Flessa, Johannes Hertel, Olav Goetz, Wolfgang Hoffmann, Stefan Teipel, Ingo Kilimann
BACKGROUND: Little is known about diagnostic work-ups or the costs of diagnosing dementia in specialized care. Here, we analyzed the costs of diagnosing dementia according to specific dementia disorders. METHODS: A prospective descriptive design was used to analyze the cost of diagnosing dementia for 120 patients with suspected dementia at a German memory clinic. The duration of clinical consultations and use of technical procedures were recorded by the memory clinic staff...
August 22, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28812438/acute-formaldehyde-exposure-induced-early-alzheimer-like-changes-in-mouse-brain
#18
Xudong Liu, Yuchao Zhang, Ruliu Wu, Meng Ye, Yuqing Zhao, Jun Kang, Ping Ma, Jinquan Li, Xu Yang
Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Although an association between AD and exposure to air pollutants has been discussed, the effects of pollutants on the functioning of the brain remain unclear. The indoor environment is where exposure to formaldehyde (FA) can occur. Whether exposure to FA contributes to the development of AD needs to be investigated. To determine the objective, C57BL/6 mice were exposed daily to FA (0, 0...
August 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28811268/antecedent-adhd-dementia-and-metabolic-dysregulation-a-u-s-based-cohort-analysis
#19
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/28805248/epigenetics-and-dna-methylomic-profiling-in-alzheimer-s-disease-and-other-neurodegenerative-diseases
#20
REVIEW
Janou A Y Roubroeks, Rebecca G Smith, Daniel L A van den Hove, Katie Lunnon
Recent studies have suggested a role for epigenetic mechanisms in the complex etiology of various neurodegenerative diseases. In this review, we discuss advances that have been made towards understanding the role of epigenetic processes in neurodegenerative disorders, with a particular focus on Alzheimer's disease, where the most extensive studies have been undertaken to date. We provide a brief overview of DNA modifications, followed by a summarization of studies of DNA modifications in Alzheimer's disease and other neurodegenerative diseases...
August 14, 2017: Journal of Neurochemistry
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