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https://www.readbyqxmd.com/read/29790502/inhibition-of-tau-derived-hexapeptide-aggregation-and-toxicity-by-a-self-assembled-cyclic-d-l-%C3%AE-peptide-conformational-inhibitor
#1
A Belostozky, M Richman, E Lisniansky, A Tovchygrechko, J H Chill, S Rahimipour
Aggregation and accumulation of amyloid β and tau proteins to plaques and neurofibrillary tangles are the key pathogenic events in Alzheimer's disease. Here, we studied the capability of the cyclic d,l-α-peptide CP-2 as a conformational inhibitor of different amyloids to cross-interact with tau-derived AcPHF6 peptide and inhibit its aggregation, membrane perturbation and toxicity.
May 23, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29782959/targeting-central-%C3%AE-2-receptors-ameliorates-streptozotocin-induced-neuroinflammation-via-inhibition-of-glycogen-synthase-kinase3-pathway-in-mice
#2
Nora O Abdel Rasheed, Nesrine S El-Sayed, Aiman S El-Khatib
Alzheimer's disease (AD) is portrayed by progressive cognitive decline and pathological deposition of amyloid plaques as well as neurofibrillary tangles. Most of AD cases are sporadic, resulting from overlap of various environmental and genetic factors. Intra-cerebroventricular injection of streptozotocin (STZ) leads to insulin resistance brain state accompanied by memory decline, oxidative stress, and neuro-degeneration which mimic the pathologies associated with sporadic Alzheimer's disease (SAD). In the current study, protective effects of formoterol in STZ-induced SAD were studied...
May 18, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29782794/peptides-peptidomimetics-and-carbohydrate-peptide-conjugates-as-amyloidogenic-aggregation-inhibitors-for-alzheimer-s-disease
#3
Philip Ryan, Bhautikkumar Patel, Vivek Makwana, Hemant Jadhav, Milton John Kiefel, Andrew Davey, Tristan Reekie, Santosh Rudrawar, Michael Kassiou
Alzheimer's disease (AD) is a progressive neurodegenerative disorder accounting for 60-80% of dementia cases. For many years, AD causality was attributed to amyloid-β (Aβ) aggregated species. Recently, multiple therapies that target Aβ aggregation have failed in clinical trials, since Aβ aggregation is found in AD and healthy patients. Attention has therefore shifted towards the aggregation of the peptide tau as a major driver of AD. Numerous inhibitors of tau-based pathology have recently been developed...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782315/tlr4-gene-expression-and-pro-inflammatory-cytokines-in-alzheimer-s-disease-and-in-response-to-hippocampal-deafferentation-in-rodents
#4
Justin Miron, Cynthia Picard, Josée Frappier, Doris Dea, Louise Théroux, Judes Poirier
One important aspect in Alzheimer's disease pathology is the presence of chronic inflammation. Considering its role as a key receptor in the microglial innate immune system, TLR4 was shown to regulate the binding and phagocytosis of amyloid plaques by microglia in several mouse models of amyloidosis, as well as the production of pro-inflammatory cytokines. To our knowledge, TLR4 and its association with cytokines have not been thoroughly examined in the brains of subjects affected with Alzheimer's disease. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in postmortem human brains, we observed increased expression for the TLR4 and TNF genes (p = 0...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#5
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29777753/characterization-of-impaired-cerebrovascular-structure-in-app-ps1-mouse-brains
#6
Kee-Chan Ahn, Cameron R Learman, Gary L Dunbar, Panchanan Maiti, Won-Cheoul Jang, Hyeon-Cheol Cha, Mee-Sook Song
Alzheimer's disease (AD) is defined by senile plaques, tauopathy and neuronal cell death in specific area of the brain. Recent studies suggest that neurovascular dysfunction may be an integral part of AD pathogenesis, contributing to the onset and development of AD pathologies such as neuronal death, inflammatory response, and breakdown of blood brain barrier (BBB). In addition, vascular complications caused by age-related metabolic diseases such as diabetes and high blood pressure have high incidence in development of dementia and AD...
May 16, 2018: Neuroscience
https://www.readbyqxmd.com/read/29777003/impact-of-reference-target-region-selection-on-amyloid-pet-standard-uptake-value-ratios-in-the-phase-1b-prime-study-of-aducanumab
#7
Ping Chiao, Barry J Bedell, Brian Avants, Alex P Zijdenbos, Marilyn Grand'Maison, Paul O'Neill, John O'Gorman, Tianle Chen, Robert Koeppe
Standardized uptake value ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid beta positron emission tomography (Aβ-PET). Here, we explore the impact of target and reference region of interest (ROI) selection on SUVR effect size using interventional data from the ongoing Phase Ib PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer's disease (AD). Methods: Florbetapir PET SUVR was calculated at baseline (screening) and Weeks 26 and 54 for patients randomized to placebo and each of four aducanumab doses (1, 3, 6, and 10 mg/kg), using whole cerebellum, cerebellar grey matter, cerebellar white matter, pons, and subcortical white matter as reference regions...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29776894/amyloid-pet-in-neurodegenerative-diseases-with-dementia
#8
V Camacho, A Gómez-Grande, P Sopena, D García-Solís, M Gómez Río, C Lorenzo, S Rubí, J Arbizu
Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive decline and memory loss, and is the most common form of dementia. Amyloid plaques with neurofibrillary tangles are a neuropathological hallmark of AD that produces synaptic dysfunction and culminates later in neuronal loss. Amyloid PET is a useful, available and non-invasive technique that provides in vivo information about the cortical amyloid burden. In the latest revised criteria for the diagnosis of AD biomarkers were defined and integrated: pathological and diagnostic biomarkers (increased retention on fibrillar amyloid PET or decreased Aβ1-42 and increased T-Tau or P-Tau in CSF) and neurodegeneration or topographical biomarkers (temporoparietal hypometabolism on 18 F-FDG PET and temporal atrophy on MRI)...
May 15, 2018: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#9
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29771571/effect-of-weak-combined-static-and-extremely-low-frequency-alternating-magnetic-fields-on-spatial-memory-and-brain-amyloid-%C3%AE-in-two-animal-models-of-alzheimer-s-disease
#10
Natalia V Bobkova, Vadim V Novikov, Natalia I Medvinskaya, Irina Y Aleksandrova, Inna V Nesterova, Eugenii E Fesenko
Subchronic effect of a weak combined magnetic field (MF), produced by superimposing a constant component, 42 µT and an alternating MF of 0.08 µT, which was the sum of two frequencies of 4.38 and 4.88 Hz, was studied in olfactory bulbectomized (OBE) and transgenic Tg (APPswe, PSEN1) mice, which were used as animal models of sporadic and heritable Alzheimer's disease (AD) accordingly. Spatial memory was tested in a Morris water maze on the following day after completion of training trials with the hidden platform removed...
May 17, 2018: Electromagnetic Biology and Medicine
https://www.readbyqxmd.com/read/29770843/patterns-and-severity-of-vascular-amyloid-in-alzheimer-s-disease-associated-with-duplications-and-missense-mutations-in-app-gene-down-syndrome-and-sporadic-alzheimer-s-disease
#11
David M A Mann, Yvonne S Davidson, Andrew C Robinson, Nancy Allen, Tadafumi Hashimoto, Anna Richardson, Matthew Jones, Julie S Snowden, Neil Pendleton, Marie-Claude Potier, Annie Laquerrière, Vee Prasher, Takeshi Iwatsubo, Andre Strydom
In this study, we have compared the severity of amyloid plaque formation and cerebral amyloid angiopathy (CAA), and the subtype pattern of CAA pathology itself, between APP genetic causes of AD (APPdup, APP mutations), older individuals with Down syndrome (DS) showing the pathology of Alzheimer's disease (AD) and individuals with sporadic (early and late onset) AD (sEOAD and sLOAD, respectively). The aim of this was to elucidate important group differences and to provide mechanistic insights related to clinical and neuropathological phenotypes...
May 16, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29760662/targeting-renin-angiotensin-system-against-alzheimer-s-disease
#12
REVIEW
Abadi Kahsu Gebre, Birhanetensay Masresha Altaye, Tesfay Mehari Atey, Kald Beshir Tuem, Derbew Fikadu Berhe
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29758264/anti-il17-treatment-ameliorates-down-syndrome-phenotypes-in-mice
#13
Noemí Rueda, Verónica Vidal, Susana García-Cerro, Josep Oriol Narcís, María Llorens-Martín, Andrea Corrales, Sara Lantigua, Marcos Iglesias, Jesús Merino, Ramón Merino, Carmen Martínez-Cué
Down syndrome (DS) is characterized by structural and functional anomalies that are present prenatally and that lead to intellectual disabilities. Later in life, the cognitive abilities of DS individuals progressively deteriorate due to the development of Alzheimer's disease (AD)-associated neuropathology (i.e., β-amyloid (Aβ) plaques, neurofibrillary tangles (NFTs), neurodegeneration, synaptic pathology, neuroinflammation and increased oxidative stress). Increasing evidence has shown that among these pathological processes, neuroinflammation plays a predominant role in AD etiopathology...
May 11, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29755842/lipopolysaccharide-endotoxemia-induces-amyloid-%C3%AE-and-p-tau-formation-in-the-rat-brain
#14
Li-Ming Wang, Qi Wu, Ryan A Kirk, Kevin P Horn, Ahmed H Ebada Salem, John M Hoffman, Jeffrey T Yap, Joshua A Sonnen, Rheal A Towner, Fernando A Bozza, Rosana S Rodrigues, Kathryn A Morton
Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS)...
2018: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29755512/proton-pump-inhibitors-and-dementia-physiopathological-mechanisms-and-clinical-consequences
#15
REVIEW
Gloria Ortiz-Guerrero, Diana Amador-Muñoz, Carlos Alberto Calderón-Ospina, Daniel López-Fuentes, Mauricio Orlando Nava Mesa
Alzheimer's disease (AD) is the most common type of dementia, mainly encompassing cognitive decline in subjects aged ≥65 years. Further, AD is characterized by selective synaptic and neuronal degeneration, vascular dysfunction, and two histopathological features: extracellular amyloid plaques composed of amyloid beta peptide (A β ) and neurofibrillary tangles formed by hyperphosphorylated tau protein. Dementia and AD are chronic neurodegenerative conditions with a complex physiopathology involving both genetic and environmental factors...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29755340/glutamate-transporter-glt1-expression-in-alzheimer-disease-and-dementia-with-lewy-bodies
#16
Paula Garcia-Esparcia, Daniela Diaz-Lucena, Marina Ainciburu, Benjamin Torrejón-Escribano, Margarita Carmona, Franc Llorens, Isidro Ferrer
Glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2), a major modulator of glutamate homeostasis in astrocytes, is assessed in post-mortem human brain samples of frontal cortex area 8 in advanced stages of Alzheimer disease (AD) and terminal stages of dementia with Lewy bodies (DLB) in order to gain understanding of astrogliopathy in diseases manifested by dementia. Glial fibrillary acidic protein (GFAP) mRNA expression is significantly increased in AD but not in DLB, whereas GLT1 , vesicular glutamate transporter 1 ( vGLUT1 ) and aldehyde dehydrogenase 1 family member 1 ( ALDH1L1 ) are not modified in AD and DLB when compared with controls...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29751990/conversion-of-iodine-to-fluorine-18-based-on-iodinated-chalcone-and-evaluation-for-%C3%AE-amyloid-pet-imaging
#17
Sho Kaide, Masahiro Ono, Hiroyuki Watanabe, Yoichi Shimizu, Yuji Nakamoto, Kaori Togashi, Aiko Yamaguchi, Hirofumi Hanaoka, Hideo Saji
In the amyloid cascade hypothesis, β-amyloid (Aβ) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [18 F]4-dimethylamino-4'-fluoro-chalcone ([18 F]DMFC) and [18 F]4'-fluoro-4-methylamino-chalcone ([18 F]FMC), as Aβ imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by 18 F-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [18 F]DMFC and [18 F]FMC...
May 3, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29751505/passive-a%C3%AE-immunotherapy-current-achievements-and-future-perspectives
#18
REVIEW
Stephan Schilling, Jens-Ulrich Rahfeld, Inge Lues, Cynthia A Lemere
Passive immunotherapy has emerged as a very promising approach for the treatment of Alzheimer’s disease and other neurodegenerative disorders, which are characterized by the misfolding and deposition of amyloid peptides. On the basis of the amyloid hypothesis, the majority of antibodies in clinical development are directed against amyloid β (Aβ), the primary amyloid component in extracellular plaques. This review focuses on the current status of Aβ antibodies in clinical development, including their characteristics and challenges that came up in clinical trials with these new biological entities (NBEs)...
May 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29748975/lysosomes-autophagosomes-and-alzheimer-pathology-in-dementia-with-lewy-body-disease
#19
Rowan Gurney, Yvonne S Davidson, Andrew C Robinson, Anna Richardson, Matthew Jones, Julie S Snowden, David M A Mann
A failure of protein degradation may underpin Lewy body disease (LBD) where α-synuclein is assimilated into the pathognomic Lewy bodies and Lewy neurites. We investigated histological alterations in lysosomes and autophagosomes in the substantia nigra (SN) and cingulate gyrus (CG) in 34 patients with LBD employing antibodies against phosphorylated α-synuclein and lysosomal (lysosomal associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2), cathepsin D (CTSD)) and autophagosomal (microtubule-associated protein light chain 3α (LC3A)) proteins...
May 10, 2018: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/29748872/two-photon-probes-for-in-vivo-multicolor-microscopy-of-the-structure-and-signals-of-brain-cells
#20
REVIEW
Clément Ricard, Erica D Arroyo, Cynthia X He, Carlos Portera-Cailliau, Gabriel Lepousez, Marco Canepari, Daniel Fiole
Imaging the brain of living laboratory animals at a microscopic scale can be achieved by two-photon microscopy thanks to the high penetrability and low phototoxicity of the excitation wavelengths used. However, knowledge of the two-photon spectral properties of the myriad fluorescent probes is generally scarce and, for many, non-existent. In addition, the use of different measurement units in published reports further hinders the design of a comprehensive imaging experiment. In this review, we compile and homogenize the two-photon spectral properties of 280 fluorescent probes...
May 11, 2018: Brain Structure & Function
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