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Amyloid plaque

Qian Cai, Prasad Tammineni
Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release...
October 20, 2016: Journal of Alzheimer's Disease: JAD
Hyeon-Joong Kim, Dae-Joong Kim, Eun-Ju Shin, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Ik-Hyun Cho, Hyoung-Chun Kim, Seung-Yeol Nah
We previously showed that gintonin, an exogenous lysophosphatidic acid (LPA) receptor ligand, attenuated β-amyloid plaque formation in the cortex and hippocampus, and restored β-amyloid-induced memory dysfunction. Both endogenous LPA and LPA receptors play a key role in embryonic brain development. However, little is known about whether gintonin can induce hippocampal cell proliferation in adult wild-type mice and an APPswe/PSEN-1 double Tg mouse model of Alzheimer's disease (AD). In the present study, we examined the effects of gintonin on the proliferation of hippocampal neural progenitor cells (NPCs) in vitro and its effects on the hippocampal cell proliferation in wild-type mice and a transgenic AD mouse model...
October 17, 2016: Neurochemistry International
Jian Yang, Jing Yang, Steven H Liang, Yungen Xu, Anna Moore, Chongzhao Ran
In brains of Alzheimer's disease (AD), reactive oxygen species (ROS) levels are significantly higher than that of healthy brains. Evidence suggests that, during AD onset and progression, a vicious cycle revolves around amyloid beta (Aβ) production, aggregation, plaque formation, microglia/immunological responses, inflammation, and ROS production. In this cycle, ROS species play a central role, and H2O2 is one of the most important ROS species. In this report, we have designed a fluorescent imaging probe CRANAD-88, which is capable of cascade amplifying near infrared fluorescence (NIRF) signals at three levels upon interacting with H2O2 in AD brains...
October 20, 2016: Scientific Reports
Zhiyou Cai, Chuanling Wang, Wenming Yang
Berberine, an important protoberberine isoquinoline alkaloid, has several pharmacological activities, including antimicrobial, glucose- and cholesterol-lowering, antitumoral, and immunomodulatory properties. Substantial studies suggest that berberine may be beneficial to Alzheimer's disease (AD) by limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles. Increasing evidence has indicated that berberine exerts a protective role in atherosclerosis related to lipid- and glucose-lowering properties, implicating that berberine has the potential to inhibit these risk factors for AD...
2016: Neuropsychiatric Disease and Treatment
D A Bangasser, H Dong, J Carroll, Z Plona, H Ding, L Rodriguez, C McKennan, J G Csernansky, S H Seeholzer, R J Valentino
Several neuropsychiatric and neurodegenerative disorders share stress as a risk factor and are more prevalent in women than in men. Corticotropin-releasing factor (CRF) orchestrates the stress response, and excessive CRF is thought to contribute to the pathophysiology of these diseases. We previously found that the CRF1 receptor (CRF1) is sex biased whereby coupling to its GTP-binding protein, Gs, is greater in females, whereas β-arrestin-2 coupling is greater in males. This study used a phosphoproteomic approach in CRF-overexpressing (CRF-OE) mice to test the proof of principle that when CRF is in excess, sex-biased CRF1 coupling translates into divergent cell signaling that is expressed as different brain phosphoprotein profiles...
October 18, 2016: Molecular Psychiatry
Rosemary J Jackson, Nikita Rudinskiy, Abigail G Herrmann, Shaun Croft, JeeSoo Monica Kim, Veselina Petrova, Juan Jose Ramos-Rodriguez, Rose Pitstick, Susanne Wegmann, Monica Garcia-Alloza, George A Carlson, Bradley T Hyman, Tara L Spires-Jones
Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined...
October 17, 2016: European Journal of Neuroscience
J M G van Bergen, X Li, J Hua, S J Schreiner, S C Steininger, F C Quevenco, M Wyss, A F Gietl, V Treyer, S E Leh, F Buck, R M Nitsch, K P Pruessmann, P C M van Zijl, C Hock, P G Unschuld
Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aβ) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aβ-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aβ-plaque-load was observable both for cortical and subcortical brain-regions...
October 17, 2016: Scientific Reports
Yanping Yang, Xuedan Wang, Hui Yang, Hualong Fu, Jinming Zhang, Xiaojun Zhang, Jiapei Dai, Zhiyong Zhang, Chunping Lin, Yuzhi Guo, Mengchao Cui
This study describes an effective strategy to improve pharmacokinetics of Aβ imaging agents, offering a novel class of (R)- and (S)-18F-labeled 2-arylbenzoheterocyclic derivatives which bear an additional chiral hydroxyl group on the side chain. These ligands displayed binding abilities toward Aβ aggregates with Ki values varying from 3.2 to 195.6 nM. Chirality-related discrepancy was observed in biodistribution and (S)-2-phenylbenzoxazole enantiomers exhibited vastly improved brain clearance with washout ratios higher than 20...
October 15, 2016: Molecular Pharmaceutics
Xiaotian T Fang, Jonas Eriksson, Gunnar Antoni, Ulrika Yngve, Linda Cato, Lars Lannfelt, Dag Sehlin, Stina Syvänen
Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) into insoluble plaques. Intermediates, Aβ oligomers (Aβo), appear to be the mechanistic cause of disease. The de facto PET AD ligand, [(11)C]PIB, binds and visualizes Aβ plaque load, which does not correlate well with disease severity. Therefore, finding a dynamic target that changes with pathology progression in AD is of great interest. Aβo alter synaptic plasticity, inhibit long-term potentiation, and facilitate long-term depression; key mechanisms involved in memory and learning...
October 12, 2016: Neuropharmacology
Farron L McIntee, Patrizia Giannoni, Steven Blais, George Sommer, Thomas A Neubert, Agueda Rostagno, Jorge Ghiso
Amyloid β (Aβ) is the major constituent of the brain deposits found in parenchymal plaques and cerebral blood vessels of patients with Alzheimer's disease (AD). Several lines of investigation support the notion that synaptic pathology, one of the strongest correlates to cognitive impairment, is related to the progressive accumulation of neurotoxic Aβ oligomers. Since the process of oligomerization/fibrillization is concentration-dependent, it is highly reliant on the homeostatic mechanisms that regulate the steady state levels of Aβ influencing the delicate balance between rate of synthesis, dynamics of aggregation, and clearance kinetics...
2016: Frontiers in Aging Neuroscience
Sonia Mazzitelli, Fabia Filipello, Marco Rasile, Eliana Lauranzano, Chiara Starvaggi-Cucuzza, Matteo Tamborini, Davide Pozzi, Isabella Barajon, Toni Giorgino, Antonino Natalello, Michela Matteoli
Substantial data indicate that amyloid-β (Aβ), the major component of senile plaques, plays a central role in Alzheimer's Disease and indeed the assembly of naturally occurring amyloid peptides into cytotoxic aggregates is linked to the disease pathogenesis. Although Aβ42 is a highly aggregating form of Aβ, the co-occurrence of shorter Aβ peptides might affect the aggregation potential of the Aβ pool. In this study we aimed to assess whether the structural behavior of human Aβ42 peptide inside the brain is influenced by the concomitant presence of N-terminal fragments produced by the proteolytic activity of glial cells...
October 10, 2016: Acta Neuropathologica Communications
O S Levin, E E Vasenina
Amyloid hypothesis of Alzheimer's disease (AD) has been long the primary one. During the 25-year history the concept has been dramatically changed. Accumulation of β-amyloid is associated not only with the disruption of its synthesis (as it seemed after the discovery of genetic mechanisms of some familial cases of AD) but rather with the disruption of its clearance and elimination from the brain tissue via the microcirculatory system. It has been recognized that soluble oligomers of β-amyloid, but not senile plaques that consisted of insoluble conjugates described by A...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Elodie Martin, Céline Boucher, Bertrand Fontaine, Cécile Delarasse
Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid-β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte-derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates...
October 8, 2016: Aging Cell
Syeda Mehpara Farhat, Touqeer Ahmed
Alzheimer's disease, a neurodegenerative disorder, is characterized by accumulation of amyloid beta (Aβ) plaques, neurofibrillary tangles and loss of cholinergic neurons. The localization of Aβ plaques particularly in the cholinergic neuron-rich areas has led to the discovery that Aβ binds to α7 nicotinic acetylcholine receptors (nAChRs) with very high affinity. This discovery has led to extensive exploration of the possible outcomes of this binding, ranging from the subcellular signaling pathways to its effects on behavioral and cognitive functions...
October 5, 2016: Current Drug Targets
Allal Boutajangout, Abdulwahab Noorwali, Hazem Atta, Thomas Wisniewski
INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia. The search for new treatments is made more urgent given its increasing prevalence resulting from the aging of the global population. Over the past two decades, stem cell technologies have become an increasingly attractive option to both study and potentially treat neurodegenerative diseases. Several investigators reported a beneficial effect of different types of stem or progenitor cells on the pathology and cognitive function in AD models...
October 4, 2016: Current Alzheimer Research
Chadwick M Hales, Eric B Dammer, Qiudong Deng, Duc M Duong, Marla Gearing, Juan C Troncoso, Madhav Thambisetty, James J Lah, Joshua M Shulman, Allan I Levey, Nicholas T Seyfried
Despite a key role of amyloid-beta (Aβ) in Alzheimer's disease (AD), mechanisms that link Aβ plaques to tau neurofibrillary tangles and cognitive decline still remain poorly understood. The purpose of this study was to quantify proteins in the sarkosyl-insoluble brain proteome correlated with Aβ and tau insolubility in the asymptomatic phase of AD (AsymAD) and through mild cognitive impairment (MCI) and symptomatic AD. Employing label-free mass spectrometry based proteomics, we quantified 2,711 sarkosyl-insoluble proteins across the prefrontal cortex from 35 individual cases representing control, AsymAD, MCI and AD...
October 8, 2016: Proteomics
F Guerriero, C Sgarlata, M Francis, N Maurizi, A Faragli, S Perna, M Rondanelli, M Rollone, G Ricevuti
Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both...
October 7, 2016: Aging Clinical and Experimental Research
Eric A Tanifum, Ketan Ghaghada, Craig Vollert, Elizabeth Head, Jason L Eriksen
No abstract text is available yet for this article.
October 4, 2016: Journal of Alzheimer's Disease: JAD
Nor Faeizah Ibrahim, Daijiro Yanagisawa, Lina Wati Durani, Hamizah Shahirah Hamezah, Hanafi Ahmad Damanhuri, Wan Zurinah Wan Ngah, Mayumi Tsuji, Yuji Kiuchi, Kenjiro Ono, Ikuo Tooyama
Alzheimer's disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-β (Aβ) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aβ aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo...
October 1, 2016: Journal of Alzheimer's Disease: JAD
Hideomi Hamasaki, Hiroyuki Honda, Tsuyoshi Okamoto, Sachiko Koyama, Satoshi O Suzuki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Toru Iwaki
BACKGROUND: The Hisayama study is a prospective cohort study of lifestyle-related diseases that commenced in 1961. Through it, a significant increasing trend in the prevalence of Alzheimer's disease has been observed over the past 18 years. OBJECTIVES: We sought to investigate the increases in brain pathology related to Alzheimer's disease using automated MATLAB morphometric analyses for quantifying tau pathology. METHODS: We examined a series of autopsied cases from Hisayama residents obtained between 1998 and 2003 (group A: 203 cases), and between 2009 and 2014 (group B: 232 cases)...
October 1, 2016: Journal of Alzheimer's Disease: JAD
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