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Alzheimer's etiologies

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https://www.readbyqxmd.com/read/28106551/conscientiousness-is-negatively-associated-with-grey-matter-volume-in-young-apoe%C3%A9-4-carriers
#1
Lukas Kunz, Martin Reuter, Nikolai Axmacher, Christian Montag
The etiology of late onset Alzheimer's disease (LOAD) depends on multiple factors, among which the APOEɛ4 allele is the most adverse genetic determinant and conscientiousness represents an influential personality trait. A potential association of both factors with brain structure in young adulthood may constitute a constellation that sets the course toward or against the subtle disease progression of LOAD that starts decades before clinical manifestation. Hence, in the present study, we examined the modulating effects of APOEɛ4 on the relation between personality dimensions, including conscientiousness, and total grey matter volume (GMV) in young healthy adults using an a priori genotyping design...
January 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28103467/-investigation-of-genetic-etiology-in-neurodegenerative-dementias-recommendations-from-the-centro-hospitalar-s%C3%A3-o-jo%C3%A3-o-neurogenetics-group
#2
João Massano, Miguel Leão, Carolina Garrett
In the past few years several gene mutations have been identified as causative of the most frequent neurodegenerative dementias (Alzheimer disease and frontotemporal dementia). These advances, along with the complex phenotype-genotype relationships and the costs associated with genetic testing, have often made it difficult for clinicians to decide with regard to a rational plan for the investigation of the genetic etiology of the degenerative dementias. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of Alzheimer disease and frontotemporal dementia in clinical practice, based on international consensus documents (currently containing partly outdated information) and published scientific evidence on this topic...
October 2016: Acta Médica Portuguesa
https://www.readbyqxmd.com/read/28102375/the-dynamic-binding-of-cholesterol-to-the-multiple-sites-of-c99-as-revealed-by-coarse-grained-and-all-atom-simulations
#3
Cheng-Dong Li, Qin Xu, Ruo-Xu Gu, Jing Qu, Dong-Qing Wei
It is generally believed that the etiology of Alzheimer's disease (AD) is closely related to the amyloid-β polypeptides, produced from γ-secretase cleavage of C99. There is preliminary evidence that cholesterol directly activates γ-secretase cleavage of C99 through mechanisms that have not been understood so far. In this article, coarse-grained (CG) and all-atom (AT) simulations were employed to investigate the association between C99 and cholesterol, which is essential for our understanding of the role of cholesterol in the amyloidogenic pathway...
January 19, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28098204/strain-specific-fibril-propagation-by-an-a%C3%AE-dodecamer
#4
Dexter N Dean, Pradipta K Das, Pratip Rana, Franklin Burg, Yona Levites, Sarah E Morgan, Preetam Ghosh, Vijayaraghavan Rangachari
Low molecular weight oligomers of amyloid-β (Aβ) have emerged as the primary toxic agents in the etiology of Alzheimer disease (AD). Polymorphism observed within the aggregation end products of fibrils are known to arise due to microstructural differences among the oligomers. Diversity in aggregate morphology correlates with the differences in AD, cementing the idea that conformational strains of oligomers could be significant in phenotypic outcomes. Therefore, it is imperative to determine the ability of strains to faithfully propagate their structure...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097204/genomics-implicates-adaptive-and-innate-immunity-in-alzheimer-s-and-parkinson-s-diseases
#5
Sarah A Gagliano, Jennie G Pouget, John Hardy, Jo Knight, Michael R Barnes, Mina Ryten, Michael E Weale
OBJECTIVES: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. METHODS: We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28094792/identification-of-a-nuclear-respiratory-factor-1-recognition-motif-in-the-apolipoprotein-e-variant-apoe4-linked-to-alzheimer-s-disease
#6
Anne Urfer-Buchwalder, Roman Urfer
Alzheimer's disease affects tens of millions of people worldwide and its prevalence continues to rise. It is caused by a combination of a subject's heredity, environment, lifestyle, and medical condition. The most significant genetic risk factor for late onset Alzheimer's disease is a variant of the apolipoprotein E gene, APOE4. Here we show that the single nucleotide polymorphism rs429358 that defines APOE4 is located in a short sequence motif repeated several times within exon 4 of apolipoprotein E, reminiscent of the structure of transcriptional enhancers...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28072821/maysin-and-its-flavonoid-derivative-from-centipedegrass-attenuates-amyloid-plaques-by-inducting-humoral-immune-response-with-th2-skewed-cytokine-response-in-the-tg-appswe-ps1de9-alzheimer-s-mouse-model
#7
Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Hyoung-Woo Bai, Seung Sik Lee, SungBeom Lee, Byung Yeoup Chung, Jae-Hyeon Cho
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models...
2017: PloS One
https://www.readbyqxmd.com/read/28065470/the-rare-variant-generalized-disequilibrium-test-for-association-analysis-of-nuclear-and-extended-pedigrees-with-application-to-alzheimer-disease-wgs-data
#8
Zongxiao He, Di Zhang, Alan E Renton, Biao Li, Linhai Zhao, Gao T Wang, Alison M Goate, Richard Mayeux, Suzanne M Leal
Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population-based designs. Moreover, some family-based designs are robust to confounding due to population admixture or substructure. We developed a RV extension of the generalized disequilibrium test (GDT) to analyze sequence data obtained from nuclear and extended families...
January 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28060279/quantitative-3d-in-silico-modeling-q3dism-of-cerebral-amyloid-beta-phagocytosis-in-rodent-models-of-alzheimer-s-disease
#9
Marie-Victoire Guillot-Sestier, Tara M Weitz, Terrence Town
Neuroinflammation is now recognized as a major etiological factor in neurodegenerative disease. Mononuclear phagocytes are innate immune cells responsible for phagocytosis and clearance of debris and detritus. These cells include CNS-resident macrophages known as microglia, and mononuclear phagocytes infiltrating from the periphery. Light microscopy has generally been used to visualize phagocytosis in rodent or human brain specimens. However, qualitative methods have not provided definitive evidence of in vivo phagocytosis...
December 26, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28059796/a-common-variant-in-the-mc1r-gene-p-v92m-is-associated-with-alzheimer-s-disease-risk
#10
Gemma Tell-Marti, Joan Anton Puig-Butille, Miriam Potrony, Estel Plana, Celia Badenas, Anna Antonell, Raquel Sanchez-Valle, José L Molinuevo, Alberto Lleó, Daniel Alcolea, Juan Fortea, Ruben Fernandez-Santiago, Jordi Clarimón, Albert Lladó, Susana Puig
Despite the recent identification of some novel risk genes for Alzheimer's disease (AD), the genetic etiology of late-onset Alzheimer's disease (LOAD) remains largely unknown. The inclusion of these novel risk genes to the risk attributable to the APOE gene accounts for roughly half of the total genetic variance in LOAD. The evidence indicates that undiscovered genetic factors may contribute to AD susceptibility. In the present study, we sequenced the MC1R gene in 525 Spanish LOAD patients and in 160 controls...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059794/oxidative-stress-synaptic-dysfunction-and%C3%A2-alzheimer-s-disease
#11
Eric Tönnies, Eugenia Trushina
Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28059790/combined-creutzfeldt-jakob-jacob-alzheimer-s-disease-cases-are-important-in-search-for-microbes-in-alzheimer-s-disease
#12
Frank O Bastian
The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28057301/axgxe-using-flies-to-interrogate-the-complex-etiology-of-neurodegenerative-disease
#13
C Burke, K Trinh, V Nadar, S Sanyal
Progressive and late-onset neurological disorders such as Parkinson's disease and Alzheimer's disease affect up to 50 million people globally-a number postulated to double every 20 years in a continually aging population. While predisposing allelic variants in several genes clearly confer risk, individual age and specific environmental influences are equally important discriminators of disease onset age and progression. However, none of these factors can independently predict disease with significant precision...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28049644/functional-prions-in-the-brain
#14
REVIEW
Joseph B Rayman, Eric R Kandel
Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes...
January 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28035920/using-drugs-as-molecular-probes-a%C3%A2-computational-chemical-biology-approach-in-neurodegenerative-diseases
#15
Mohammad Asif Emran Khan Emon, Alpha Tom Kodamullil, Reagon Karki, Erfan Younesi, Martin Hofmann-Apitius
Neurodegenerative diseases including Alzheimer's disease are complex to tackle because of the complexity of the brain, both in structure and function. Such complexity is reflected by the involvement of various brain regions and multiple pathways in the etiology of neurodegenerative diseases that render single drug target approaches ineffective. Particularly in the area of neurodegeneration, attention has been drawn to repurposing existing drugs with proven efficacy and safety profiles. However, there is a lack of systematic analysis of the brain chemical space to predict the feasibility of repurposing strategies...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28033505/transgenerational-transmission-of-an-anticholinergic-endophenotype-with-memory-dysfunction
#16
Wolfram Doehner, Lieselotte Praße, James Wolpers, Martina K Brückner, Uwe Ueberham, Thomas Arendt
Impaired cholinergic neurotransmission associated with cognitive dysfunction occurs in various mental disorders of different etiologies including Alzheimer's disease and postalcoholic dementia and others. To address the question whether there exists a common endophenotype with a defined genetic and/or epigenetic signature causing mental dysfunction in these disorders, we investigated 2 generations of offspring born to alcohol-treated mothers. Here, we show that memory impairment and reduced synthesis of acetylcholine occurs in both F1 (exposed to ethanol in utero) and F2 generation (never been exposed to ethanol)...
December 5, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28029715/the-association-of-antidepressant-drug-usage-with-cognitive-impairment-or-dementia-including-alzheimer-disease-a-systematic-review-and-meta-analysis
#17
John Moraros, Chijioke Nwankwo, Scott B Patten, Darrell D Mousseau
OBJECTIVE: To determine if antidepressant drug usage is associated with cognitive impairment or dementia, including Alzheimer disease (AD). METHOD: We conducted a systematic search of Medline, PubMed, PsycINFO, Web of Science, Embase, CINAHL, and the Cochrane Library. An initial screen by abstracts and titles was performed, and relevant full articles were then reviewed and assessed for their methodologic quality. Crude effect estimates were extracted from the included articles and a pooled estimate was obtained using a random effects model...
December 28, 2016: Depression and Anxiety
https://www.readbyqxmd.com/read/28026168/synthetic-models-of-quasi-stable-amyloid-%C3%AE-40-oligomers-with-significant-neurotoxicity
#18
Yumi Irie, Kazuma Murakami, Mizuho Hanaki, Yusuke Hanaki, Takashi Suzuki, Yoko Monobe, Tomoyo Takai, Ken-Ichi Akagi, Taiji Kawase, Kenji Hirose, Kazuhiro Irie
The formation of soluble oligomers of amyloid β42 and 40 (Aβ42, Aβ40) is the initial event in the pathogenesis of Alzheimer's disease (AD). Based on previous systematic proline replacement and solid-state NMR, we proposed a toxic dimer structure of Aβ42, a highly aggregative alloform, with a turn at positions 22 and 23, and a hydrophobic core in the C-terminal region. However, in addition to Aβ42, Aβ40 dimers can also contribute to AD progression because of the more abundance of Aβ40 monomer in biological fluids...
January 12, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28004338/network-analysis-identifies-disease-specific-pathways-for-parkinson-s-disease
#19
Chiara Monti, Ilaria Colugnat, Leonardo Lopiano, Adriano Chiò, Tiziana Alberio
Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis...
December 21, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27989508/a-multi-network-approach-identifies-protein-specific-co-expression-in-asymptomatic-and-symptomatic-alzheimer-s-disease
#20
Nicholas T Seyfried, Eric B Dammer, Vivek Swarup, Divya Nandakumar, Duc M Duong, Luming Yin, Qiudong Deng, Tram Nguyen, Chadwick M Hales, Thomas Wingo, Jonathan Glass, Marla Gearing, Madhav Thambisetty, Juan C Troncoso, Daniel H Geschwind, James J Lah, Allan I Levey
Here, we report proteomic analyses of 129 human cortical tissues to define changes associated with the asymptomatic and symptomatic stages of Alzheimer's disease (AD). Network analysis revealed 16 modules of co-expressed proteins, 10 of which correlated with AD phenotypes. A subset of modules overlapped with RNA co-expression networks, including those associated with neurons and astroglial cell types, showing altered expression in AD, even in the asymptomatic stages. Overlap of RNA and protein networks was otherwise modest, with many modules specific to the proteome, including those linked to microtubule function and inflammation...
December 14, 2016: Cell Systems
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