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https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#1
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28197669/clearance-of-cerebral-a%C3%AE-in-alzheimer-s-disease-reassessing-the-role-of-microglia-and-monocytes
#2
REVIEW
Leah Zuroff, David Daley, Keith L Black, Maya Koronyo-Hamaoui
Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer's disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aβ is a complex process mediated by various systems and cell types, including vascular transport across the blood-brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28193995/evaluating-the-effectiveness-of-gtm-1-rapamycin-and-carbamazepine-on-autophagy-and-alzheimer-disease
#3
Lijuan Zhang, Lina Wang, Run Wang, Yuan Gao, Haoyue Che, Yonghua Pan, Peng Fu
BACKGROUND This study was proposed to compare the efficacy and safety of GTM-1, Rapamycin (Rap), and Carbamazepine (CBZ) in managing Alzheimer disease (AD). The impact of the above mentioned therapeutic drugs on autophagy was also investigated in our study. MATERIAL AND METHODS Firstly, 3×Tg AD mice were randomly allocated into 4 groups (each group with 10 mice), in which AD mice were separately treated with dimethylsulfoxide (DMSO, vehicle group), GTM-1 (6 mg/kg), Rap (1 mg/kg), and CBZ (100 mg/kg). Then spatial memory and learning ability of mice was tested using the Morris water maze...
February 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28193538/multifunctional-luv-liposomes-decorated-for-bbb-and-amyloid-targeting-a-in-vitro-proof-of-concept
#4
Konstantina Papadia, Eleni Markoutsa, Spyridon Mourtas, Anastassios Giannou, Barabara La Ferla, Fransesco Nicotra, Mario Salmona, Pavlos Klepetsanis, Georgios T Stathopoulos, Sophia G Antimisiaris
Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential...
February 10, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28188218/focal-solute-trapping-and-global-glymphatic-pathway-impairment-in-a-murine-model-of-multiple-microinfarcts
#5
Minghuan Wang, Fengfei Ding, SaiYue Deng, Xuequn Guo, Wei Wang, Jeffrey J Iliff, Maiken Nedergaard
Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. Yet the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid beta and tau...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28179468/neurofilament-as-a-blood-marker-for-diagnosis-and-monitoring-of-primary-progressive-aphasias
#6
Petra Steinacker, Elisa Semler, Sarah Anderl-Straub, Janine Diehl-Schmid, Matthias L Schroeter, Ingo Uttner, Hans Foerstl, Bernhard Landwehrmeyer, Christine A F von Arnim, Jan Kassubek, Patrick Oeckl, Hans-Jürgen Huppertz, Klaus Fassbender, Klaus Fliessbach, Johannes Prudlo, Carola Roßmeier, Johannes Kornhuber, Anja Schneider, Alexander E Volk, Martin Lauer, Adrian Danek, Albert C Ludolph, Markus Otto
OBJECTIVE: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. METHODS: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ1-42), tau, and phosphorylated tau...
February 8, 2017: Neurology
https://www.readbyqxmd.com/read/28167277/purification-of-recombinant-c-reactive-protein-mutants
#7
Avinash Thirumalai, Sanjay K Singh, David J Hammond, Toh B Gang, Donald N Ngwa, Asmita Pathak, Alok Agrawal
C-reactive protein (CRP) is an evolutionarily conserved protein, a component of the innate immune system, and an acute phase protein in humans. In addition to its raised level in blood in inflammatory states, CRP is also localized at sites of inflammation including atherosclerotic lesions, arthritic joints and amyloid plaque deposits. Results of in vivo experiments in animal models of inflammatory diseases indicate that CRP is an anti-pneumococcal, anti-atherosclerotic, anti-arthritic and an anti-amyloidogenic molecule...
February 3, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28164774/tauopathies-focus-on-changes-at-the-neurovascular-unit
#8
Alena Michalicova, William A Banks, Jaroslav Legath, Andrej Kovac
In the past, the blood-brain barrier (BBB) had been characterized mainly as a layer of endothelial cells forming the vessel/capillary wall of the brain. More recently, the BBB is considered to be a part of a highly dynamic and interactive system called the neurovascular unit (NVU), consisting of vascular cells, glial cells, and neurons. The list of central nervous system (CNS) pathologies involving BBB dysfunction is rapidly growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to host of processes resulting in progressive synaptic and neuronal dysfunction and loss...
February 3, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28161476/markers-of-neuroinflammation-associated-with-alzheimer-s-disease-pathology-in-older-adults
#9
Julius Popp, Aikaterini Oikonomidi, Domilė Tautvydaitė, Loïc Dayon, Michael Bacher, Eugenia Migliavacca, Hugues Henry, Richard Kirkland, India Severin, Jérôme Wojcik, Gene L Bowman
BACKGROUND: In vitro and animal studies have linked neuroinflammation to Alzheimer's disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline. OBJECTIVE: To identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i...
February 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28161339/amyloid-%C3%AE-related-angiitis-a-report-of-two-cases-with-unusual-presentations
#10
Denise W Ng, Shino Magaki, Kevin H Terashima, Adrienne M Keener, Noriko Salamon, Stellios Karnezis, Luke Macyszyn, Harry V Vinters
Amyloid-β related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy in which amyloid-β (Aβ) deposition in the leptomeningeal and cortical vessels is associated with vasculitis characterized by transmural lymphohistiocytic, often granulomatous, inflammation. Patients usually present with acute to subacute cognitive dysfunction, headaches, and focal neurologic deficits. We report two cases of ABRA with unusual clinical presentations, including one case with fatal cerebral edema leading to herniation and Duret hemorrhages, and another associated with both lobar and deep parenchymal hemorrhages with intraventricular extension as well as hypercoagulability...
February 1, 2017: Human Pathology
https://www.readbyqxmd.com/read/28143625/potential-benefits-of-phytochemicals-against-alzheimer-s-disease
#11
Emma L Wightman
Our current therapeutic drugs for Alzheimer's disease are predominantly derived from the alkaloid class of plant phytochemicals. These drugs, such as galantamine and rivastigmine, attenuate the decline in the cholinergic system but, as the alkaloids occupy the most dangerous end of the phytochemical spectrum (indeed they function as feeding deterrents and poisons to other organisms within the plant itself), they are often associated with unpleasant side effects. In addition, these cholinesterase inhibiting alkaloids target only one system in a disorder, which is typified by multifactorial deficits...
February 1, 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28143622/effects-of-the-duration-of-hyperlipidemia-on-cerebral-lipids-vessels-and-neurons-in-rats
#12
Weichun Yang, He Shi, Jianfen Zhang, Ziyi Shen, Guangyu Zhou, Minyu Hu
BACKGROUND: The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention. METHOD: One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0...
January 31, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28140480/acute-phase-proteins-and-iron-status-in-cats-with-chronic-kidney-disease
#13
R Javard, C Grimes, L Bau-Gaudreault, M Dunn
BACKGROUND: The role of inflammation in the development and progression of chronic kidney disease (CKD) in cats is not well characterized. Hepcidin is a recently discovered acute-phase protein (APP) that plays an important role in iron metabolism and contributes to the development of anemia in humans with CKD. OBJECTIVES: To compare serum APP concentrations, iron status, and erythropoietin (EPO) concentrations in healthy cats and cats with naturally occurring CKD...
January 31, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28138429/evaluation-of-early-phase-18-f-florbetaben-pet-acquisition-in-clinical-routine-cases
#14
Sonja Daerr, Matthias Brendel, Christian Zach, Erik Mille, Dorothee Schilling, Mathias Johannes Zacherl, Katharina Bürger, Adrian Danek, Oliver Pogarell, Andreas Schildan, Marianne Patt, Henryk Barthel, Osama Sabri, Peter Bartenstein, Axel Rominger
OBJECTIVES: In recent years several [(18)F]-labelled amyloid PET tracers have been developed and have obtained clinical approval. There is accumulating evidence that early (post injection) acquisitions with these tracers are equally informative as conventional blood flow and metabolism studies for diagnosis of Alzheimer's disease, but there have been few side-by-side studies. Therefore, we investigated the performance of early acquisitions of [(18)F]-florbetaben (FBB) PET compared to [(18)F]-fluorodeoxyglucose (FDG) PET in a clinical setting...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28131710/dl-3-n-butylphthalide-edaravone-hybrids-as-novel-dual-inhibitors-of-amyloid-%C3%AE-aggregation-and-monoamine-oxidases-with-high-antioxidant-potency-for-alzheimer-s-therapy
#15
Xiaoming Qiang, Yan Li, Xia Yang, Li Luo, Rui Xu, Yunxiaozhu Zheng, Zhongcheng Cao, Zhenghuai Tan, Yong Deng
Considering the complex etiology of Alzheimer's disease (AD), multifunctional agents may be beneficial for the treatment of this disease. A series of DL-3-n-butylphthalide-Edaravone hybrids were designed, synthesized and evaluated as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases. Among them, compounds 9a-d exhibited good inhibition of self-induced Aβ1-42 aggregation with inhibition ratio 57.7-71.5%. For MAO, these new hybrids exhibited good balance of inhibition for MAO-A and MAO-B...
January 17, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28131239/immune-and-inflammatory-biomarkers-in-cases-of-bovine-perinatal-mortality-with-and-without-infection-in-utero
#16
Paulina Jawor, Tadeusz Stefaniak, John F Mee
The objective of this study was to compare acute-phase protein [serum amyloid A (SAA) and haptoglobin (Hp)] and immunoglobulin G1 and M concentrations in blood plasma of cases of bovine perinatal mortality due to infection in utero or traumotocia and in unexplained cases. Plasma samples were collected from 110 stillborn calves with bacterial infection (INF_B, n = 16), with viral or parasitic infection (INF_V/P, n = 31) during pregnancy, with lesions of fatal traumotocia (TRAUM, n = 22), and from unexplained deaths (UNEXPL, n = 41)...
February 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28131209/potential-oxidative-stress-biomarkers-of-mild-cognitive-impairment-due-to-alzheimer-disease
#17
REVIEW
Ana García-Blanco, Miguel Baquero, Máximo Vento, Esperanza Gil, Luis Bataller, Consuelo Cháfer-Pericás
The high and increasing incidence of Alzheimer Disease (AD) worldwide is a major global concern. Classical diagnosis is carried out in the dementia phase, often in the moderate stages when treatment efficacy is limited. Nowadays, early diagnosis, even in pre-dementia stages, is possible in selected cases within an appropriate clinical setting, employing cerebral spinal fluid (CSF) sample analysis and neuroimaging procedures. In spite of the accurate diagnosis achieved by novel CSF biomarkers or positron emission tomography beta-amyloid tracers, these tests are invasive and expensive...
February 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28130465/phenotype-and-neuroimaging-in-cerebral-amyloid-angiopathy-more-blood
#18
Mark O McCarron, Eric E Smith
No abstract text is available yet for this article.
January 27, 2017: Neurology
https://www.readbyqxmd.com/read/28129943/beta-site-amyloid-precursor-protein-cleaving-enzyme-1-inhibition-impairs-synaptic-plasticity-via-seizure-protein-6
#19
Kaichuan Zhu, Xianyuan Xiang, Severin Filser, Petar Marinković, Mario M Dorostkar, Sophie Crux, Ulf Neumann, Derya R Shimshek, Gerhard Rammes, Christian Haass, Stefan F Lichtenthaler, Jenny M Gunnersen, Jochen Herms
BACKGROUND: Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a promising drug target for the treatment of Alzheimer's disease. Prolonged BACE1 inhibition interferes with structural and functional synaptic plasticity in mice, most likely by altering the metabolism of BACE1 substrates. Seizure protein 6 (SEZ6) is predominantly cleaved by BACE1, and Sez6 knockout mice share some phenotypes with BACE1 inhibitor-treated mice. We investigated whether SEZ6 is involved in BACE1 inhibition-induced structural and functional synaptic alterations...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28129888/alzheimer-s-disease-innate-immunity-gone-awry
#20
Theodore B VanItallie
Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline...
January 11, 2017: Metabolism: Clinical and Experimental
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