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Cerebral amyloid

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https://www.readbyqxmd.com/read/28526436/intracranial-il-17a-overexpression-decreases-cerebral-amyloid-angiopathy-by-upregulation-of-abca1-in-an-animal-model-of-alzheimer-s-disease
#1
Junling Yang, Jinghong Kou, Robert Lalonde, Ken-Ichiro Fukuchi
Neuroinflammation is a pervasive feature of Alzheimer's disease (AD) and characterized by activated microglia, increased proinflammatory cytokines and/or infiltrating immune cells. T helper 17 (Th17) cells are found in AD brain parenchyma and interleukin-17A (IL-17A) is identified around deposits of aggregated amyloid β protein (Aβ). However, the role of IL-17A in AD pathogenesis remains elusive. We overexpressed IL-17A in an AD mouse model via recombinant adeno-associated virus serotype 5 (rAAV5)-mediated intracranial gene delivery...
May 17, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28515043/brain-perivascular-macrophages-initiate-the-neurovascular-dysfunction-of-alzheimer-a%C3%AE-peptides
#2
Laibaik Park, Ken Uekawa, Lidia Garcia-Bonilla, Kenzo Koizumi, Michelle Murphy, Rose Pitstick, Linda H Younkin, Steven G Younkin, Ping Zhou, Geroge A Carlson, Josef Anrather, Costantino Iadecola
Rationale: Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer's disease (AD), the leading cause of late-life dementia. The amyloid-β peptide (Aβ), a key pathogenic factor in AD, induces profound alterations in neurovascular regulation through the innate immunity receptor CD36, which, in turn, activates a Nox2-containing NADPH oxidase leading to cerebrovascular oxidative stress. Brain perivascular macrophages (PVM) located in the perivascular space, a major site of brain Aβ collection and clearance, are juxtaposed to the wall of intracerebral resistance vessels and are a powerful source of reactive oxygen species (ROS)...
May 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#3
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28512130/combination-therapy-with-octyl-gallate-and-ferulic-acid-improves-cognition-and-neurodegeneration-in-a-transgenic-mouse-model-of-alzheimer-disease
#4
Takashi Mori, Naoki Koyama, Jun Tan, Tatsuya Segawa, Masahiro Maeda, Terrence Town
To date, there is no effective Alzheimer disease (AD) modifying therapy. Nonetheless, combination therapy holds promise, and nutraceuticals (natural dietary compounds with therapeutic properties) and their synthetic derivatives are well-tolerated candidates. We tested whether combination therapy with octyl gallate (OG) and ferulic acid (FA) improves cognition and mitigates AD-like pathology in the PSAPP transgenic mouse model of cerebral amyloidosis. One-year-old mice with established β-amyloid plaques received daily doses of OG and FA alone or in combination for 3 months...
May 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511918/molecular-imaging-of-serotonin-degeneration-in-mild-cognitive-impairment
#5
Gwenn S Smith, Frederick S Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin J Sodums, Christopher M Marano, Cynthia A Munro, Jason Brandt, Michael A Kraut, Yun Zhou, Dean F Wong, Clifford I Workman
Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions, as well as the cell bodies of origin (raphe nuclei)...
May 13, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28509380/amyloid-is-essential-but-insufficient-for-alzheimer-causation-addition-of-subcellular-cofactors-is-required-for-dementia
#6
REVIEW
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28505976/in-vivo-detection-of-gray-matter-neuropathology-in-the-3xtg-mouse-model-of-alzheimer-s-disease-with-diffusion-tensor-imaging
#7
Wanda M Snow, Ryan Dale, Zoe O'Brien-Moran, Richard Buist, Danial Peirson, Melanie Martin, Benedict C Albensi
A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinical symptoms, efforts to detect brain changes early could significantly enhance our ability to diagnose AD sooner. Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude, orientation, and anisotropy of the diffusion of water in tissues, has been used to infer neuropathological changes in vivo...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28502044/hippocampal-proteomic-analysis-reveals-distinct-pathway-deregulation-profiles-at-early-and-late-stages-in-a-rat-model-of-alzheimer-s-like-amyloid-pathology
#8
Sonia Do Carmo, Gogce Crynen, Tiffany Paradis, Jon Reed, M Florencia Iulita, Adriana Ducatenzeiler, Fiona Crawford, A Claudio Cuello
The cerebral accumulation and cytotoxicity of amyloid beta (Aβ) is central to Alzheimer's pathogenesis. However, little is known about how the amyloid pathology affects the global expression of brain proteins at different disease stages. In order to identify genotype and time-dependent significant changes in protein expression, we employed quantitative proteomics analysis of hippocampal tissue from the McGill-R-Thy1-APP rat model of Alzheimer-like amyloid pathology. McGill transgenic rats were compared to wild-type rats at early and late pathology stages, i...
May 13, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28501451/habitual-exercise-levels-are-associated-with-cerebral-amyloid-load-in-presymptomatic-autosomal-dominant-alzheimer-s-disease
#9
Belinda M Brown, Hamid R Sohrabi, Kevin Taddei, Samantha L Gardener, Stephanie R Rainey-Smith, Jeremiah J Peiffer, Chengjie Xiong, Anne M Fagan, Tammie Benzinger, Virginia Buckles, Kirk I Erickson, Roger Clarnette, Tejal Shah, Colin L Masters, Michael Weiner, Nigel Cairns, Martin Rossor, Neill R Graff-Radford, Stephen Salloway, Jonathan Vöglein, Christoph Laske, James Noble, Peter R Schofield, Randall J Bateman, John C Morris, Ralph N Martins
INTRODUCTION: The objective of this study was to evaluate the relationship between self-reported exercise levels and Alzheimer's disease (AD) biomarkers, in a cohort of autosomal dominant AD mutation carriers. METHODS: In 139 presymptomatic mutation carriers from the Dominantly Inherited Alzheimer Network, the relationship between self-reported exercise levels and brain amyloid load, cerebrospinal fluid (CSF) Aβ42, and CSF tau levels was evaluated using linear regression...
May 11, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28499154/mutation-of-the-kunitz-type-proteinase-inhibitor-domain-in-the-amyloid-%C3%AE-protein-precursor-abolishes-its-anti-thrombotic-properties-in-vivo
#10
Feng Xu, Judianne Davis, Michael Hoos, William E Van Nostrand
INTRODUCTION: Kunitz proteinase inhibitor (KPI) domain-containing forms of the amyloid β-protein precursor (AβPP) inhibit cerebral thrombosis. KPI domain-lacking forms of AβPP are abundant in brain. Regions of AβPP other than the KPI domain may also be involved with regulating cerebral thrombosis. To determine the contribution of the KPI domain to the overall function of AβPP in regulating cerebral thrombosis we generated a reactive center mutant that was devoid of anti-thrombotic activity and studied its anti-thrombotic function in vitro and in vivo...
May 4, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28497179/detectable-neuropsychological-differences-in-early-preclinical-alzheimer-s-disease-a-meta-analysis
#11
REVIEW
S Duke Han, Caroline P Nguyen, Nikki H Stricker, Daniel A Nation
The development of methods for in vivo detection of cerebral beta amyloid retention and tau accumulation have been increasingly useful in characterizing preclinical Alzheimer's disease (AD). While the association between these biomarkers and eventual AD has been demonstrated among cognitively intact older adults, the link between biomarkers and neurocognitive ability remains unclear. We conducted a meta-analysis to test the hypothesis that cognitively intact older adults would show statistically discernable differences in neuropsychological performance by amyloid status (amyloid negative = A-, amyloid positive = A+)...
May 11, 2017: Neuropsychology Review
https://www.readbyqxmd.com/read/28494436/neuronal-tetraploidization-in-the-cerebral-cortex-correlates-with-reduced-cognition-in-mice-and-precedes-and-recapitulates-alzheimer-s-associated-neuropathology
#12
Noelia López-Sánchez, Ángela Fontán-Lozano, Anna Pallé, Valentina González-Álvarez, Alberto Rábano, José L Trejo, José M Frade
A controversy exists as to whether de novo-generated neuronal tetraploidy (dnNT) occurs in Alzheimer's disease. In addition, the presence of age-associated dnNT in the normal brain remains unexplored. Here we show that age-associated dnNT occurs in both superficial and deep layers of the cerebral cortex of adult mice, a process that is blocked in the absence of E2F1, a known regulator of cell cycle progression. This blockage correlates with improved cognition despite compromised neurogenesis in the adult hippocampus was confirmed in mice lacking the E2f1 gene...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28489317/pharmacogenomics-of-angiotensin-receptor-neprilysin-inhibitor-and-its-long-term-side-effects
#13
REVIEW
Chayakrit Krittanawong, Takeshi Kitai
The development of the promising agent sacubitril/valsartan, known as an angiotensin receptor blocker-neprilysin inhibitor (ARNI), to improve heart failure (HF) management, may benefit morbidity, mortality, and readmission rates in patients with HF. The PARADIGM-HF trial demonstrated that the ARNI can reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), while ongoing PARAMOUNT and PARAGON-HF trials determined whether the ARNI has morbidity and mortality benefits in patients with heart failure with preserved ejection fraction (HFpEF)...
May 10, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28488154/impact-of-multiple-pathologies-on-the-threshold-for-clinically-overt-dementia
#14
REVIEW
Alifiya Kapasi, Charles DeCarli, Julie A Schneider
Longitudinal clinical-pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development of Alzheimer's disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis)...
May 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28485779/effects-of-vitamin-b12-on-postoperative-cognitive-dysfunction-induced-by-isoflurane-anesthesia-in-rats
#15
H-Y Sha, J-B Zhao, M-X Sha, S-M Guo
OBJECTIVE: Postoperative cognitive dysfunction is a clinical syndrome associated with cognitive decline in patients after anesthesia. This study aimed to investigate the effect of VB12 (Vitamin B12), a kind of necessary micronutrients promoting the growth and development of the nervous system, on cognitive dysfunction induced by isoflurane anesthesia. MATERIALS AND METHODS: Eighteen-month-old rats were exposed to or were not exposed to 1.4% isoflurane for 2 h. Two hours before isoflurane exposure, rats in groups with VB12 were injected intramuscularly with VB12 at 10 or 20 μg...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28482635/the-anti-amyloid-%C3%AE-and-neuroprotective-properties-of-a-novel-tricyclic-pyrone-molecule
#16
Izumi Maezawa, Bende Zou, Jacopo Di Lucente, William S Cao, Conrado Pascual, Sahani Weerasekara, Man Zhang, Xinmin Simon Xie, Duy H Hua, Lee-Way Jin
There is an urgent unmet need for new therapeutics for Alzheimer's disease (AD), the most common cause of dementia in the elderly. Therapeutic approaches targeting amyloid-β (Aβ) and its downstream toxicities have become major strategies in AD drug development. We have taken a rational design approach and synthesized a class of tricyclic pyrone (TP) compounds that show anti-Aβ and other neuroprotective actions. The in vivo efficacy of a lead TP named CP2 to ameliorate AD-like pathologies has been shown in mouse models...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28482213/brain-predicted-age-in-down-syndrome-is-associated-with-beta-amyloid-deposition-and-cognitive-decline
#17
James H Cole, Tiina Annus, Liam R Wilson, Ridhaa Remtulla, Young T Hong, Tim D Fryer, Julio Acosta-Cabronero, Arturo Cardenas-Blanco, Robert Smith, David K Menon, Shahid H Zaman, Peter J Nestor, Anthony J Holland
Individuals with Down syndrome (DS) are more likely to experience earlier onset of multiple facets of physiological aging. This includes brain atrophy, beta amyloid deposition, cognitive decline, and Alzheimer's disease-factors indicative of brain aging. Here, we employed a machine learning approach, using structural neuroimaging data to predict age (i.e., brain-predicted age) in people with DS (N = 46) and typically developing controls (N = 30). Chronological age was then subtracted from brain-predicted age to generate a brain-predicted age difference (brain-PAD) score...
April 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28478826/novel-aspects-of-defensins-involvement-in-virus-induced-autoimmunity-in-the-central-nervous-system
#18
Evangelos I Kazakos, Jannis Kountouras, Stergios A Polyzos, Georgia Deretzi
Recent research on re-circulation of interstitial fluid from the brain parenchyma to the periphery and its inferred importance in immune surveillance dysregulation are changing our conceptualization of the pathophysiology of virus-induced autoimmunity. In this context, it is necessary to reassess the immunomodulatory properties of human defensins that are variably expressed by cerebral microglia, astrocytes and choroid plexus epithelial cells and exhibit complex and often confounding roles in neuroinflammatory processes...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28476760/distribution-of-lacunes-in-cerebral-amyloid-angiopathy-and-hypertensive-small-vessel-disease
#19
Marco Pasi, Gregoire Boulouis, Panagiotis Fotiadis, Eitan Auriel, Andreas Charidimou, Kellen Haley, Alison Ayres, Kristin M Schwab, Joshua N Goldstein, Jonathan Rosand, Anand Viswanathan, Leonardo Pantoni, Steven M Greenberg, M Edip Gurol
OBJECTIVE: To evaluate whether the burden of deep and lobar lacunes differs between patients with intracerebral hemorrhage (ICH) with definite/probable cerebral amyloid angiopathy (CAA) per the Boston criteria and hypertensive small vessel disease (HTN-SVD; ICH in basal ganglia, thalami, brainstem). METHODS: We defined lobar and deep lacunes similar to the topographic distribution used for ICH and cerebral microbleeds (CMBs). We then compared their distribution between patients with CAA-ICH and those with strictly deep CMB and ICH (HTN-ICH)...
May 5, 2017: Neurology
https://www.readbyqxmd.com/read/28476757/lacunes-black-holes-in-our-understanding-of-cerebral-amyloid-angiopathy
#20
EDITORIAL
Eric E Smith, Jin-Moo Lee
No abstract text is available yet for this article.
May 5, 2017: Neurology
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