Β-Amyloid in Alzheimer's Disease Initiation and Phenotypic
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Little Proteins, Big Clues After a Quarter of a Century, the Amyloid Hypothesis for Alzheimer’S Disease Is Reconnecting to Its Roots in Prion Research
ALZHEIMER’S DISEASE OUTLOOK SIMON FRASER/JAMES KING-HOLMES/SCIENCE PHOTO LIBRARY PHOTO KING-HOLMES/SCIENCE SIMON FRASER/JAMES At autopsy, the brains of Alzheimer’s patients (right) are filled with amyloid plaques, reminiscent of the plaques seen in the brains of animals with scrapie (left). AMYLOID Little proteins, big clues After a quarter of a century, the amyloid hypothesis for Alzheimer’s disease is reconnecting to its roots in prion research. BY JIM SCHNABEL It is easy to forget how recently Alzheimer’s resembling those seen in scrapie, often sur- disease entered the public consciousness. rounded by dying neurons and their twisted n September 1984, a group of prominent For many decades after it first appeared in the axons and dendrites. When doused with Congo researchers from around the world met in medical literature, the term referred only to red, a standard pathology stain, and illumi- Scotland to discuss a disease that afflicted an obscure, early onset form of dementia. nated with polarized light, the Alzheimer’s Isheep and goats. What we now know as common, late-onset plaques — just like scrapie plaques — displayed Scrapie, as they called it, was important Alzheimer’s was then called ‘senile dementia’ — an apple-green shimmer, a prismatic sign of the for more than agricultural reasons — it was and it was so prevalent among the elderly that hydrogen bonds that held their fibrils tightly also the most easily studied example of an it hardly seemed worth classifying as a disease together. Protein aggregates that had this emerging class of diseases that destroyed (see ‘A problem for our age’, page S2). -
Improving the Gene Ontology Resource to Facilitate More Informative Analysis and Interpretation of Alzheimer’S Disease Data
G C A T T A C G G C A T genes Article Improving the Gene Ontology Resource to Facilitate More Informative Analysis and Interpretation of Alzheimer’s Disease Data Barbara Kramarz 1 , Paola Roncaglia 2 , Birgit H. M. Meldal 2 , Rachael P. Huntley 1 , Maria J. Martin 2, Sandra Orchard 2, Helen Parkinson 2, David Brough 3, Rina Bandopadhyay 4, Nigel M. Hooper 3 and Ruth C. Lovering 1,* 1 UCL Institute of Cardiovascular Science, University College London, Rayne Building, 5 University Street, London WC1E 6JF, UK; [email protected] (B.K.); [email protected] (R.P.H.) 2 European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK; [email protected] (P.R.); [email protected] (B.H.M.M.); [email protected] (M.J.M.); [email protected] (S.O.); [email protected] (H.P.) 3 Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK; [email protected] (D.B.); [email protected] (N.M.H.) 4 UCL Queen Square Institute of Neurology and Reta Lila Weston Institute of Neurological Studies, 1 Wakefield Street, London WC1N 1PJ, UK; [email protected] * Correspondence: [email protected] or [email protected]; Tel.: +44-207-679-6965 Received: 31 October 2018; Accepted: 23 November 2018; Published: 29 November 2018 Abstract: The analysis and interpretation of high-throughput datasets relies on access to high-quality bioinformatics resources, as well as processing pipelines and analysis tools. -
Copper Toxicity Links to Pathogenesis of Alzheimer's Disease And
International Journal of Molecular Sciences Review Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches Hafza Wajeeha Ejaz 1, Wei Wang 2 and Minglin Lang 1,3,* 1 CAS Center for Excellence in Biotic Interactions, College of Life Science, University of Chinese Academy of Sciences, Yuquan Road 19, Beijing 100049, China; [email protected] 2 School of Medical and Health Sciences, Edith Cowan University, Perth WA6027, Australia; [email protected] 3 College of Life Science, Agricultural University of Hebei, Baoding 071000, China * Correspondence: [email protected]; Tel.: +86-10-8825-6585/6967-2639 Received: 25 August 2020; Accepted: 29 September 2020; Published: 16 October 2020 Abstract: Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. -
Possible Causes of Alzheimer's Disease Related Amyloid-Β
Possible Causes of Alzheimer’s Disease Related Amyloid-β Plaques and Neurofibrillary Tangles Rochelle Rubinstein Rochelle Rubinstein will graduate with a BS in Biology in January 2018. Abstract Alzheimer’s disease is a major cause of dementia in the elderly and is a global health concern. However, researchers are not sure what causes the characteristic amyloid-β plaque accumulation and neurofibrillary tangles in the brain. Several model mechanisms have been proposed to answer this question. This paper examines three of these possibilities. Research suggests that a particular allele of the apoE gene is responsible for the neurodegeneration found in Alzheimer’s disease. Another hypothesis is that the mechanism of Alzheimer’s is related to prion-mediated protein misfolding. Other studies indicate that certain environmental factors can cause the neuropathology of Alzheimer’s. Specifically, this paper will investigate the effects of a neurotoxin produced by cyanobacteria. Each of these possibilities is backed by supporting evidence, and there is probably not just one cause. Alzheimer’s is a complex disease caused by a combination of inter- acting factors that may include these models, as well as others that have not been focused on in this paper. The more that is discovered about the multiple possible causes of Alzheimer’s, the closer we are to developing ways of preventing these pathways in the hope of a cure. Introduction from a transmembrane protein called amyloid precursor protein Alzheimer’s disease is the most common cause of dementia in the (APP). Different enzymes called alpha-secretase, beta-secretase, elderly (Seeley, Miller 2015) and a devastating disease for those af- and gamma-secretase can cleave the APP protein in different plac- fected and their families. -
Extracellular Amyloid Deposits in Alzheimer's and Creutzfeldt
International Journal of Molecular Sciences Review Extracellular Amyloid Deposits in Alzheimer’s and Creutzfeldt–Jakob Disease: Similar Behavior of Different Proteins? Nikol Jankovska 1,*, Tomas Olejar 1 and Radoslav Matej 1,2,3 1 Department of Pathology and Molecular Medicine, Third Faculty of Medicine, Charles University and Thomayer Hospital, 100 00 Prague, Czech Republic; [email protected] (T.O.); [email protected] (R.M.) 2 Department of Pathology, First Faculty of Medicine, Charles University, and General University Hospital, 100 00 Prague, Czech Republic 3 Department of Pathology, Third Faculty of Medicine, Charles University, and University Hospital Kralovske Vinohrady, 100 00 Prague, Czech Republic * Correspondence: [email protected]; Tel.: +42-026-108-3102 Abstract: Neurodegenerative diseases are characterized by the deposition of specific protein aggre- gates, both intracellularly and/or extracellularly, depending on the type of disease. The extracellular occurrence of tridimensional structures formed by amyloidogenic proteins defines Alzheimer’s disease, in which plaques are composed of amyloid β-protein, while in prionoses, the same term “amyloid” refers to the amyloid prion protein. In this review, we focused on providing a detailed di- dactic description and differentiation of diffuse, neuritic, and burnt-out plaques found in Alzheimer’s disease and kuru-like, florid, multicentric, and neuritic plaques in human transmissible spongiform encephalopathies, followed by a systematic classification of the morphological similarities and differ- ences between the extracellular amyloid deposits in these disorders. Both conditions are accompanied by the extracellular deposits that share certain signs, including neuritic degeneration, suggesting a particular role for amyloid protein toxicity. Keywords: Alzheimer’s disease; Creutzfeldt–Jakob disease; Gerstmann–Sträussler–Scheinker syn- drome; amyloid; senile plaques; PrP plaques; plaque subtypes Citation: Jankovska, N.; Olejar, T.; Matej, R. -
Optical Imaging of Beta-Amyloid Plaques in Alzheimer's Disease
biosensors Review Optical Imaging of Beta-Amyloid Plaques in Alzheimer’s Disease Ziyi Luo, Hao Xu, Liwei Liu, Tymish Y. Ohulchanskyy and Junle Qu * Center for Biomedical Photonics, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China; [email protected] (Z.L.); [email protected] (H.X.); [email protected] (L.L.); [email protected] (T.Y.O.) * Correspondence: [email protected] Abstract: Alzheimer’s disease (AD) is a multifactorial, irreversible, and incurable neurodegenerative disease. The main pathological feature of AD is the deposition of misfolded β-amyloid protein (Aβ) plaques in the brain. The abnormal accumulation of Aβ plaques leads to the loss of some neuron functions, further causing the neuron entanglement and the corresponding functional damage, which has a great impact on memory and cognitive functions. Hence, studying the accumulation mechanism of Aβ in the brain and its effect on other tissues is of great significance for the early diagnosis of AD. The current clinical studies of Aβ accumulation mainly rely on medical imaging techniques, which have some deficiencies in sensitivity and specificity. Optical imaging has recently become a research hotspot in the medical field and clinical applications, manifesting noninvasiveness, high sensitivity, absence of ionizing radiation, high contrast, and spatial resolution. Moreover, it is now emerging as a promising tool for the diagnosis and study of Aβ buildup. This review focuses on the application of the optical imaging technique for the determination of Aβ plaques in AD research. In addition, recent advances and key operational applications are discussed. Keywords: optical imaging; β-amyloid protein (Aβ); Alzheimer’s disease (AD); fluorescence mi- croscopy; nonlinear optical imaging Citation: Luo, Z.; Xu, H.; Liu, L.; Ohulchanskyy, T.Y.; Qu, J. -
Glossary of Key Brain Science Terms
A Glossary of Key Brain Science Terms www.dana.org keep in touch (Italicized terms are defined within this glossary.) Aadrenal glands: Located on top of each kidney, these two glands are involved in the body’s response to stress and help regulate growth, blood glucose levels, and the body’s metabolic rate. They receive signals from the brain and secrete several different hormones in response, including cortisol and adrenaline. adrenaline: Also called epinephrine, this hormone is secreted by the adrenal glands in response to stress and other challenges to the body. The release of adrenaline causes a number of changes throughout the body, including the metabolism of carbohydrates to supply the body’s energy demands. allele: One of the variant forms of a gene at a particular location on a chromosome. Differing alleles produce variation in inherited characteristics such as hair color or blood type. A dominant allele is one whose physiological function—such as making hair blonde—is manifest even when only a single copy is present (among the two copies of each gene that everyone inherits from their parents). A recessive allele is one that manifests only when two copies are present. amino acid: A type of small organic molecule. Amino acids have a variety of biological roles, but are best known as the “building blocks” of proteins. amino acid neurotransmitters: The most prevalent neurotransmitters in the brain, these include gluta- mate and aspartate, which have excitatory actions, and glycine and gamma-amino butyric acid (GABA), which have inhibitory actions. amygdala: Part of the brain’s limbic system, this primitive brain structure lies deep in the center of the brain and is involved in emotional reactions, such as anger, as well as emotionally charged memories. -
Microglia in Alzheimer's Disease
REVIEW SERIES: GLIA AND NEURODEGENERATION The Journal of Clinical Investigation Series Editors: Marco Colonna and David Holtzmann Microglia in Alzheimer’s disease Heela Sarlus1,2 and Michael T. Heneka1,2,3 1Department of Neurodegenerative Diseases and Gerontopsychiatry, University of Bonn, Bonn, Germany. 2Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Bonn, Germany. 3Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. Microglia are brain-resident myeloid cells that mediate key functions to support the CNS. Microglia express a wide range of receptors that act as molecular sensors, which recognize exogenous or endogenous CNS insults and initiate an immune response. In addition to their classical immune cell function, microglia act as guardians of the brain by promoting phagocytic clearance and providing trophic support to ensure tissue repair and maintain cerebral homeostasis. Conditions associated with loss of homeostasis or tissue changes induce several dynamic microglial processes, including changes of cellular morphology, surface phenotype, secretory mediators, and proliferative responses (referred to as an “activated state”). Activated microglia represent a common pathological feature of several neurodegenerative diseases, including Alzheimer’s disease (AD). Cumulative evidence suggests that microglial inflammatory activity in AD is increased while microglial-mediated clearance mechanisms are compromised. Microglia are perpetually engaged in a mutual -
CSF Protein Dynamics in Murine Models of A-Synucleinopathy and Cerebral B-Amyloidosis
CSF protein dynamics in murine models of a-synucleinopathy and cerebral b-amyloidosis Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften der Mathematisch-Naturwissenschaftlichen Fakultät und der Medizinischen Fakultät der Eberhard-Karls-Universität Tübingen vorgelegt von Timo Eninger aus Bad Saulgau, Deutschland November 2017 Tag der mündlichen Prüfung: 13.11.2017 Dekan der Math.-Nat. Fakultät: Prof. Dr. W. Rosenstiel Dekan der Medizinischen Fakultät: Prof. Dr. I. B. Autenrieth 1. Berichterstatter: Prof. Dr. M. Jucker 2. Berichterstatter: Prof. Dr. B. Maček Prüfungskommission: Prof. Dr. M. Jucker Prof. Dr. B. Maček Dr. D. David Prof. Dr. P. Heutink Erklärung Ich erkläre hiermit, dass ich die zur Promotion eingereichte Arbeit mit dem Titel: “CSF protein dynamics in murine models of a-synucleinopathy and cerebral b-amyloidosis” selbstständig verfasst, nur die angegebenen Quellen und Hilfsmittel benutzt und wörtlich oder inhaltlich übernommene Stellen als solche gekennzeichnet habe. Ich versichere an Eides statt, dass diese Angaben wahr sind und dass ich nichts verschwiegen habe. Mir ist bekannt, dass die falsche Abgabe einer Versicherung an Eides statt mit Freiheitsstrafe bis zu drei Jahren oder einer Geldstrafe bestraft wird. Tübingen, den 18. Juli 2017 Unterschrift Für Elisabeth, meine Eltern und Elena “No great mind has ever existed without a touch of madness.” - Aristotele Summary Parkinson’s (PD) and Alzheimer’s disease (AD) are the two most common neurodegen- erative diseases and of growing importance for the rapidly aging population of indus- trialized countries. A common feature of both diseases is the progressive accumulation of proteins in insoluble aggregates, which are considered to play a fundamental role in the pathogeneses ultimately resulting in marked neuronal loss. -
Annual Report 2017
CENTER OF NEUROLOGY TÜBINGEN Annual Report 2017 APPENDIX Content ANNUAL REPORT 2017 Appendix U NIVERSITY HOSPITAL OF NEUROLOGY DEPARTMENT OF NEUROLOGY WITH NEUROVASCULAR MEDICINE AND NEURO-ONCOLOGY DEPARTMENT OF NEUROLOGY AND EPILEPTOLOGY DEPARTMENT OF NEURODEGENERATIVE DISEASES DEPARTMENT OF COGNITIVE NEUROLOGY DEPARTMENT OF CELLULAR NEUROLOGY INDEPENDENT RESEARCH GROUPS PUBLICATIONS AND STUDENT TRAINING IN 2017 University Hospital of Neurology Clinical Staff WARD 46 WARD 43 Diana Arko Luther Basa HEAD OF NURSING SERVICES Annette Eisele Meike Besser Karl Andrew Gallar Önder Bilen Dr. Renate D. Fuhr Joann Gallo Roslyn Chin (Head of Nursing Services) Corinna Kalmbach Friedhelm Chmell Gabriele Kern-Braun Michelle Dupke Doris Stenske-Bader Renate Maier-Korneck Rebecca Fais (Deputy Head of Nursing Services) Bettina Mollenhauer Maria Flohr Lisa Nickel Jay Carl Garcia Adriana Hurcikova Iris Sadowski Alice Hoffmann (Division Manager, Ward 46/24/27) Sarah Schneider Tobias Illhardt Ulrike Schweizer Eva Kern Olga Krämer Gudrun Siegl Dorothe Pacholleck (Deputy Division Manager, Birgit Weimar Nicole Steiner Ward 46/24/27) Sina Westbomke Christine Reuter (Ward Manager, Ward 20) Gerda Weise (Deputy Ward Manager, 20) 4 ANNUAL REPORT 2017 WaRD 44 WaRD 45 CASE/OCCUPANCY INTENSIVE CaRE/ MANAGEMENT STROKE UNIT Jane Buo Johanna Eisele Silvia Clement Andrea Albrecht Isaac Emwinghare Christine Rebenschütz Nina Begemann Tatjana Graz Christina Tomschitz Karin Brunner Fatima Hammami Isabel Utsch-Selinow Abrar Döger Werner Hansen Laura Gabriele Sigrid Herter Tobias -
Neuronal Localization of Presenilin-1 and Association with Amyloid Plaques and Neurofibrillary Tangles in Alzheimer’S Disease
The Journal of Neuroscience, July 1, 1997, 17(13):5101–5107 Neuronal Localization of Presenilin-1 and Association with Amyloid Plaques and Neurofibrillary Tangles in Alzheimer’s Disease Jorge Busciglio,1 Henrike Hartmann,1 Alfredo Lorenzo,1 Caine Wong,1 Karlheinz Baumann,2 Bernd Sommer,2 Matthias Staufenbiel,2 and Bruce A. Yankner1 1Department of Neurology, Harvard Medical School and Division of Neuroscience, The Children’s Hospital, Boston, Massachusetts 02115, and 2Preclinical Research, Sandoz Pharma Ltd., CH-4002 Basel, Switzerland Mutations in the presenilin-1 (PS1) gene is a cause of early- highly specific antibody to the PS1 C-terminal loop domain but onset familial Alzheimer’s disease (AD). Endogenous PS1 is not with an antibody to the PS1 N terminus. This observation is associated with the endoplasmic reticulum in the cell body of consistent with a potential association of the PS1 C-terminal undifferentiated SH-SY5Y neuroblastoma cells. At early stages fragment with NFTs, because PS1 is constitutively cleaved to of neuronal differentiation in rat hippocampal culture, PS1 ap- N- and C-terminal fragments in neurons. These results suggest pears in all neuritic processes and in growth cones. In mature that PS1 is highly expressed and broadly distributed during differentiated neurons, PS1 is concentrated in the somatoden- early stages of neuronal differentiation, consistent with a role for dritic compartment but is also present at lower levels in axons. PS1 in neuronal differentiation. Furthermore, the co-localization A similar localization of PS1 is observed in vivo in neurons of the of PS1 with NFTs and plaque dystrophic neurites implicates a adult human cerebral cortex. -
Repurposing Diabetes Drugs to Treat Insulin Resistance in Alzheimer’S Disease
The Science Journal of the Lander College of Arts and Sciences Volume 10 Number 2 Spring 2017 - 2017 Repurposing Diabetes Drugs to Treat Insulin Resistance in Alzheimer’s Disease Yael Lazarus Touro College Follow this and additional works at: https://touroscholar.touro.edu/sjlcas Part of the Nervous System Diseases Commons, Nutritional and Metabolic Diseases Commons, and the Therapeutics Commons Recommended Citation Lazarus, Y. (2017). Repurposing Diabetes Drugs to Treat Insulin Resistance in Alzheimer’s Disease. The Science Journal of the Lander College of Arts and Sciences, 10(2). Retrieved from https://touroscholar.touro.edu/sjlcas/vol10/iss2/4 This Article is brought to you for free and open access by the Lander College of Arts and Sciences at Touro Scholar. It has been accepted for inclusion in The Science Journal of the Lander College of Arts and Sciences by an authorized editor of Touro Scholar. For more information, please contact [email protected]. Repurposing Diabetes Drugs to Treat Insulin Resistance in Alzheimer’s Disease Yael Lazarus Yael Lazarus graduated with a BS in Biology in January 2017 and will attend Touro Manhattan’s PA program in September 2017. Abstract Alzheimer’s disease is a neurodegenerative condition which results in a significant decline in cognitive status. Novel treatment approaches for Alzheimer’s are sorely needed, as current medications for the disease offer only marginal clinical benefit. Research has discovered a connection between the pathology of Alzheimer’s and Type 2 Diabetes, two serious and seemingly unrelated disorders. Clinical studies have shown that Alzheimer’s disease is associated with brain insulin resistance similar to the pathology of Type 2 Diabetes.