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Alzheimer's etiologies

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https://www.readbyqxmd.com/read/29332049/free-heme-and-amyloid-%C3%AE-a-fatal-liaison-in-alzheimer-s-disease
#1
Elisabeth Chiziane, Henriette Telemann, Martin Krueger, Juliane Adler, Jürgen Arnhold, A Alia, Jörg Flemmig
While the etiology of Alzheimer's disease (AD) is still unknown, an increased formation of amyloid-β (Aβ) peptide and oxidative processes are major pathological mechanism of the disease. The interaction of Aβ with free heme leads to the formation of peroxidase-active Aβ-heme complexes. However, enzyme-kinetic data and systematic mutational studies are still missing. These aspects were addressed in this study to evaluate the role of Aβ-heme complexes in AD. The enzyme-kinetic measurements showed peroxidase-specific pH- and H2O2-dependencies...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29329108/cracking-novel-shared-targets-between-epilepsy-and-alzheimer-s-disease-need-of-the-hour
#2
Nitika Garg, Rupa Joshi, Bikash Medhi
Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures...
January 12, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29328926/dna-damage-associated-oligodendrocyte-degeneration-precedes-amyloid-pathology-and-contributes-to-alzheimer-s-and-dementia
#3
Kai-Hei Tse, Aifang Cheng, Fulin Ma, Karl Herrup
INTRODUCTION: In looking for novel non-amyloid-based etiologies for Alzheimer's disease, we explore the hypothesis that age-related myelin loss is an attractive explanation for age-associated cognitive decline and dementia. METHODS: We performed a meta-analysis of data in the National Alzheimer's Coordinating Center database accompanied by quantitative histopathology of myelin and oligodendrocytes (OLs) in frontal cortices of 24 clinically characterized individuals...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29320772/a-perfect-storm-the-role-of-the-mammalian-target-of-rapamycin-mtor-in-cerebrovascular-dysfunction-of-alzheimer-s-disease-a-mini-review
#4
Candice E Van Skike, Veronica Galvan
Cerebrovascular dysfunction is detected prior to the onset of cognitive and histopathological changes in Alzheimer's disease (AD). Increasing evidence indicates a critical role of cerebrovascular dysfunction in the initiation and progression of AD. Recent studies identified the mechanistic/mammalian target of rapamycin (mTOR) as a critical effector of cerebrovascular dysfunction in AD. mTOR has a key role in the regulation of metabolism, but some mTOR-dependent mechanisms are uniquely specific to the regulation of cerebrovascular function...
January 11, 2018: Gerontology
https://www.readbyqxmd.com/read/29318973/relevance-of-follow-up-in-patients-with-core-clinical-criteria-for-alzheimer-disease-and-normal-csf-biomarkers
#5
Olivier Vercruysse, Claire Paquet, Audrey Gabelle, Xavier Delbeuck, Frederic Blanc, David Wallon, Julien Dumurgier, Eloi Magnin, Olivier Martinaud, Barbara Jung, Olivier Bousiges, Sylvain Lehmann, Constance Delaby, Muriel Quillard-Murain, Katell Peoc'h, Jean-Louis Laplanche, Elodie Bouaziz-Amar, Didier Hannequin, Bernard Sablonniere, Luc Buee, Jacques Hugon, Susanna Schraen, Florence Pasquier, Stephanie Bombois
BACKGROUND: Few patients with a normal cerebrospinal fluid (CSF) biomarker profile fulfill the clinical criteria for Alzheimer disease (AD). OBJECTIVE: The aim of this study was to test the hypothesis of misdiagnoses for these patients. METHOD: Patients from the e-PLM centers fulfilling the core clinical criteria for probable AD dementia or mild cognitive impairment due to AD (AD-MCI), with normal CSF A1-42, T-tau and P-tau biomarkers and clinical follow-up, were included...
January 9, 2018: Current Alzheimer Research
https://www.readbyqxmd.com/read/29318587/new-perspectives-on-the-role-of-melatonin-in-human-sleep-circadian-rhythms-and-their-regulation
#6
REVIEW
N Zisapel
In mammals a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24h light-dark cycle to invigorate and optimize the internal temporal order. The SCN-activated, light- inhibited production of melatonin conveys the message of darkness to the clock and induces night state in physiological function, e.g., sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo-controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, e...
January 10, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29315574/palmitate-induced-c-ebp-homologous-protein-activation-leads-to-nf-%C3%AE%C2%BAb-mediated-increase-in-bace1-activity-and-amyloid-beta-genesis
#7
Gurdeep Marwarha, Jared Schommer, Jonah Lund, Trevor Schommer, Othman Ghribi
The etiology of Alzheimer's disease (AD) is egregiously comprehended, but epidemiological studies have posited that diets rich in the saturated fatty acid palmitic acid (palmitate) are a significant risk factor. The production and accumulation of Amyloid-beta peptide (Aβ) is considered the core pathological molecular event in the pathogenesis of AD. The rate limiting step in Aβ genesis from Amyloid-β precursor protein (AβPP) is catalyzed by the enzyme β-site APP cleaving enzyme 1 (BACE1), the expression and enzymatic activity of which is significantly upregulated in the AD brain...
January 6, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29301530/understanding-amd-by-analogy-systematic-review-of-lipid-related-common-pathogenic-mechanisms-in-amd-ad-as-and-gn
#8
REVIEW
Qinyuan Xu, Sijia Cao, Sanjeeva Rajapakse, Joanne A Matsubara
RATIONALE: Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly. Due to its complex etiology, current treatments have been insufficient. Previous studies reveal three systems closely involved in AMD pathogenesis: lipid metabolism, oxidation and inflammation. These systems are also involved in Alzheimer's disease, atherosclerosis and glomerulonephritis. Understanding commonalities of these four diseases may provide insight into AMD etiology...
January 4, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29301075/characterization-of-proteins-present-in-isolated-senile-plaques-from-alzheimer-s-diseased-brains-by-maldi-tof-ms-with-ms-ms
#9
Andrea Renee Kelley, George Perry, Stephan B H Bach
The increase of insoluble senile plaques in the brain is a primary hallmark of Alzheimer's disease. The usefulness of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with tandem MS for the characterization of senile plaques from AD brains and the relevance of the components identified to furthering AD research using MS is discussed. 33 components were reproducibly observed within tryptic aliquots of senile plaques from two different AD brains after sample preparation optimization...
January 4, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29298895/endoplasmic-reticulum-stress-responses-in-mouse-models-of-alzheimer-disease-overexpression-paradigm-versus-knock-in-paradigm
#10
Shoko Hashimoto, Ayano Ishii, Naoko Kamano, Naoto Watamura, Takashi Saito, Toshio Oshima, Makoto Yokosuka, Takaomi C Saido
Endoplasmic reticulum (ER) stress is believed to play an important role in the etiology of Alzheimer disease (AD). The accumulation of misfolded proteins and perturbation of intracellular calcium homeostasis are thought to underlie the induction of ER stress, resulting in neuronal dysfunction and cell death. Several reports have shown an increased ER stress response in amyloid precursor protein (APP) and presenilin1 (PS1) double transgenic (Tg) AD mouse models. However, it remains unclear whether the ER stress observed in these mouse models is actually caused by AD pathology...
January 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29287687/an-overview-of-the-possible-therapeutic-role-of-sumoylation-in-the-treatment-of-alzheimer-s-disease
#11
REVIEW
S Marcelli, E Ficulle, L Piccolo, M Corbo, M Feligioni
Nowadays, Alzheimer's disease (AD) is recognized as a multifactorial neurological pathology whose complexity is the cause of our still low achievements in the understanding of the associated mechanisms as well the discovery of a possible definitive cure. Clinicians are aware of the few possibilities offered by medicine to cure Alzheimer's patients, restore their memory and take them back to normal life. Unfortunately, the therapeutic tools available today are not able to contrast the pathology. In the last years the tendency of the research is to formulate new hypotheses that can help to develop future effective drugs...
December 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29241829/the-aged-rhesus-macaque-manifests-braak-stage-iii-iv-alzheimer-s-like-pathology
#12
Constantinos D Paspalas, Becky C Carlyle, Shannon Leslie, Todd M Preuss, Johanna L Crimins, Anita J Huttner, Christopher H van Dyck, Douglas L Rosene, Angus C Nairn, Amy F T Arnsten
INTRODUCTION: An animal model of late-onset Alzheimer's disease is needed to research what causes degeneration in the absence of dominant genetic insults and why the association cortex is particularly vulnerable to degeneration. METHODS: We studied the progression of tau and amyloid cortical pathology in the aging rhesus macaque using immunoelectron microscopy and biochemical assays. RESULTS: Aging macaques exhibited the same qualitative pattern and sequence of tau and amyloid cortical pathology as humans, reaching Braak stage III/IV...
December 11, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29233183/restoring-synaptic-plasticity-and-memory-in-mouse-models-of-alzheimer-s-disease-by-pkr-inhibition
#13
Kyoung-Doo Hwang, Myeong Seong Bak, Sang Jeong Kim, Sangmyung Rhee, Yong-Seok Lee
Alzheimer's disease (AD) is a neurodegenerative disorder associated with deficits in cognition and synaptic plasticity. While accumulation of amyloid β (Aβ) and hyper-phosphorylation of tau are parts of the etiology, AD can be caused by a large number of different genetic mutations and other unknown factors. Considering such a heterogeneous nature of AD, it would be desirable to develop treatment strategies that can improve memory irrespective of the individual causes. Reducing the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) was shown to enhance long-term memory and synaptic plasticity in naïve mice...
December 13, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29228711/at-seeming-safe-concentrations-synergistic-effects-of-pm2-5-and-formaldehyde-co-exposure-induces-alzheimer-like-changes-in-mouse-brain
#14
Xudong Liu, Yuchao Zhang, Chen Luo, Jun Kang, Jinquan Li, Kun Wang, Ping Ma, Xu Yang
Alzheimer's disease (AD) is a serious, common, global disease, yet its etiology and pathogenesis are incompletely understood. Air pollution is a multi-pollutants co-exposure system, which may affect brain. The indoor environment is where exposure to both air particulate matter (<2.5 μm in diameter) (PM2.5) and formaldehyde (FA) can occur simultaneously. Whether exposure to such a multi-pollutant (PM2.5 plus FA) mixture contributes to the development of AD, and whether there is a difference between exposure to PM2...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224965/concerted-action-of-dipeptidyl-peptidase-iv-and-glutaminyl-cyclase-results-in-formation-of-pyroglutamate-modified-amyloid-peptides-in-vitro
#15
Alvard Antonyan, Dagmar Schlenzig, Stephan Schilling, Marcel Naumann, Svetlana Sharoyan, Sona Mardanyan, Hans-Ulrich Demuth
Compelling evidence suggests a crucial role of amyloid beta peptides (Aβ(1-40/42)) in the etiology of Alzheimer's disease (AD). The N-terminal truncation of Aβ(1-40/42) and their modification, e.g. by glutaminyl cyclase (QC), is expected to enhance the amyloid toxicity. In this work, the MALDI-TOF mass spectrometry application proved N-terminal cleavage of Aβ(1-40/42) by purified dipeptidyl peptidase IV (DPPIV) in vitro observed earlier. The subsequent transformation of resulted Aβ(3-40/42) to pE-Aβ(3-40/42) in QC catalyzed glutamate cyclization was manifested...
December 7, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29222591/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-current-concepts-and-controversies
#16
REVIEW
Kurt A Jellinger
Dementia with Lewy bodies (DLB) and Parkinson's disease-dementia (PDD), although sharing many clinical, neurochemical and morphological features, according to DSM-5, are two entities of major neurocognitive disorders with Lewy bodies of unknown etiology. Despite considerable clinical overlap, their diagnosis is based on an arbitrary distinction between the time of onset of motor and cognitive symptoms: dementia often preceding parkinsonism in DLB and onset of cognitive impairment after onset of motor symptoms in PDD...
December 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29220677/a-powerful-approach-to-estimating-annotation-stratified-genetic-covariance-via-gwas-summary-statistics
#17
Qiongshi Lu, Boyang Li, Derek Ou, Margret Erlendsdottir, Ryan L Powles, Tony Jiang, Yiming Hu, David Chang, Chentian Jin, Wei Dai, Qidu He, Zefeng Liu, Shubhabrata Mukherjee, Paul K Crane, Hongyu Zhao
Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits' genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29201555/background-and-distribution-of-lobar-microbleeds-in-cognitive-dysfunction
#18
Hirofumi Matsuyama, Yuichiro Ii, Masayuki Maeda, Maki Umino, Yukito Ueda, Ken-Ichi Tabei, Hirotaka Kida, Masayuki Satoh, Akihiro Shindo, Akira Taniguchi, Ryosuke Takahashi, Hidekazu Tomimoto
Objectives: Cerebral microbleeds (CMBs) are often observed in memory clinic patients. It has been generally accepted that deep CMBs (D-CMBs) result from hypertensive vasculopathy (HV), whereas strictly lobar CMBs (SL-CMBs) result from cerebral amyloid angiopathy (CAA) which frequently coexists with Alzheimer's disease (AD). Mixed CMBs (M-CMBs) have been partially attributed to HV and also partially attributed to CAA. The aim of this study was to elucidate the differences between SL-CMBs and M-CMBs in terms of clinical features and regional distribution...
November 2017: Brain and Behavior
https://www.readbyqxmd.com/read/29197649/heritable-genotype-contrast-mining-reveals-novel-gene-associations-specific-to-autism-subgroups
#19
Matt Spencer, Nicole Takahashi, Sounak Chakraborty, Judith Miles, Chi-Ren Shyu
Though the genetic etiology of autism is complex, our understanding can be improved by identifying genes and gene-gene interactions that contribute to the development of specific autism subtypes. Identifying such gene groupings will allow individuals to be diagnosed and treated according to their precise characteristics. To this end, we developed a method to associate gene combinations with groups with shared autism traits, targeting genetic elements that distinguish patient populations with opposing phenotypes...
November 29, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/29197200/conscious-attention-defect-and-inhibitory-control-deficit-in-parkinson-s-disease-mild-cognitive-impairment-a-comparison-study-with-amnestic-mild-cognitive-impairment-multiple-domain
#20
Davide Maria Cammisuli, Marco Timpano Sportiello
BACKGROUND: Frontal/executive dysfunction commonly occurs in Parkinso's disease - Mild Cognitive Impairment (PD-MCI patients). However, to date, the number of studies comparing PD-MCI and MCI patients of other etiologies are too small. The present study aims at clarifying the attention/working memory and executive dysfunction of PD-MCI patients in comparison to amnestic MCI multiple domain patients with first extended then abbreviated structural brain changes suggesting preclinical Alzheimer's Disease...
December 2017: Psychiatria Danubina
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