First European Congress on Hereditary ATTR Amyloidosis Paris, France

Total Page:16

File Type:pdf, Size:1020Kb

First European Congress on Hereditary ATTR Amyloidosis Paris, France Orphanet Journal of Rare Diseases 2015, Volume 10 Suppl 1 http://www.ojrd.com/content/10/S1/I1 MEETING ABSTRACTS Open Access First European Congress on Hereditary ATTR amyloidosis Paris, France. 2-3 November 2015 Published: 2 November 2015 These abstracts are available online at http://www.ojrd.com/supplements/10/S1 INVITED SPEAKER PRESENTATIONS Rice ASC, Rowbotham M, Sena E, Siddall P, Smith B, Wallace M: Pharmacotherapy for neuropathic pain in adults: systematic review, meta- Lancet Neurol I1 analysis and NeuPSIG recommendations. 2015, 14:162-73. Symptomatic therapy in ATTR amyloidosis: pain killers in TTR-FAP Nadine Attal I2 INSERM U-987, Centre dÂ’’Evaluation et de Traitement de la Douleur, CHU Neuropathic phenotypes and natural history of FAP Ambroise Parc APHP, F-92100 Boulogne-Billancourt, France and University David Adams Versailles Saint-Quentin, Versailles, F-78035, France Centre Paris-Sud, APHP, Hopital de Bicetre and Centre de Reference National E-mail: [email protected] des Neuropathies Amyloides Familiales, 94275 Le Kremlin-Bicetre, France Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):I1 Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):I2 Familial amyloidosis typically causes a nerve length-dependent small fiber TTR-FAP have been described more than 60 years ago by Corino Andrade polyneuropathy that starts in the feet with loss of temperature and pain in Porto (Brain, 1952). This peculiar disease affected many families with an sensations, associated with autonomic dysfunction, which can be extremely autosomal dominant transmission, in the third decade of life, characterized severe and life threatening. Neuropathic pain is commonly associated with by a progressive peripheral neuropathy starting in the lower extremities amyloid neuropathy. There are no randomized controlled trials in peripheral with initial impairment of thermal and pain sensibilities associated with neuropathies specifically related to familial amyloidosis. However meta- gastrointestinal disorders and loss of weight. Natural history has been analyses have confirmed that the efficacy of drugs against neuropathic pain reported by Paula Coutinho (1980) with progression in 3 stages of the generally is not linked to the aetiology of pain and therefore the drugs found disease : stage 1, a disease limited to the lower limbs and a patient is still effective in other painful polyneuropathies may benefit to patients with walking without any help (5.6 years), stage II progressive motor loss in the amyloid neuropathies [1]. Recently the Neuropathic Pain Special Interest lower limbs with steppage needing help for walking (4.8 years), and a Group (NeuPSIG) of the International Association for the Study of Pain has stage III in which the patient is bedridden or confined to a wheelchair updated evidence-based recommendations for pharmacotherapy of (2.3 years). Death comes within an average time of 10.8 years. Late onset neuropathic pain [1] using the Grading of Recommendations Assessment, (LO>50 years) cases of V30M were reported in the 2000’s, with a different Development, and Evaluation (GRADE) system. Pregabalin, gabapentin, phenotype marked by all sensory modalities involvement, relatively mild serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants autonomic symptoms, predominantly in male patients and sporadic cases particularly duloxetine, and tricyclic antidepressants (TCAs) received strong (50%). Three new phenotypes have been described in late onset cases GRADE recommendations for use and are recommended as first-line for more recently: upper limb onset neuropathy, ataxic neuropathy and motor peripheral neuropathic pain, although with caution as regards TCAs. Capsaicin neuropathy. In LO V30M, there is an earliest and rapid impact on high concentration patches, lidocaine patches and tramadol received weak locomotion, need for aid for walking within 3 years from onset, and a GRADE recommendation for use and are recommended as generally second shorter survival 7.3 years (Koike et al, JNNP 2012). There is genotype line for peripheral neuropathic pain and local pain generator. Strong opioids impact on severity and progression of the neuropathy and a correlation of and botulinum toxin type A (BTX-A received weak GRADE recommendations Neuropathy Impairment Scores (NIS) and locomotion score PND (Adams for use mainly because of efficacy in most trials but safety concerns (opioids) et al, Neurology 2015 ; Mariani et al, in press). The phenotype variety, or lower quality of evidence (BTX-A). These drugs are recommended as third frequent absence of family history and autonomic dysfunction in late line by specialist use as regards BTX-A. There was a weak GRADE onset cases contribute to delay diagnosis. The early and increase uptake of recommendation against the use of oromucosal cannabinoids (Sativex) and TTR gene testing should allow to increase the identification of TTR-FAP. valproate and strong GRADE recommendations against the use of levetiracetam and mexiletine because of generally negative results and safety concerns (mexiletine). Other drug treatments (e.g. other antiepileptics, I3 antidepressants and topical treatments, tapentadol and NMDA antagonists) or Which assessment for the carriers: the cardiac view combination therapy received inconclusive GRADE recommendations because Arnt V Kristen of generally discrepant findings, although some of these drugs might be Amylodosis Center, Department of Cardiology, University of Heidelberg, effectiveinsubgroupsofpatients.Thesedrugscanberecommendedin Germany familial amyloid neuropathy, but topical agents have a major advantage in Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):I3 this context because of their low risk of systemic side effects. Reference Cardiac manifestation is common in transthyretin-related (ATTR) 1. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, amyloidosis. However, the age of onset of first symptoms ranges widely. Haanpaa M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SR, Moreover, it differs between the individual mutations. © 2015 Attal This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated. Orphanet Journal of Rare Diseases 2015, Volume 10 Suppl 1 Page 2 of 41 http://www.ojrd.com/content/10/S1/I1 Potential treatment options to disrupt amyloid fibrils are lacking and order to select relevant articles. Additionally, clinical experience achieved cardiac manifestation is associated with poor prognosis. Thus, early by lead investigators and our own experience was applied in this analysis. identification of patients at risk for development of systemic ATTR Results: Nowadays siRNA (Patisaran®), Antisense Oligonucleotides, amyloidosis is crucial to avoid deterioration of organ function and Diflunisal and Doxycicline-TUDCA are under clinical trial investigation. maintain quality of life. Predictive moleculargenetic testing of family Election criteria definition is essential to enroll a patient in one of those members is the initial step to identify a patient at risk for hereditary ATTR clinical trials. Based on the bibliography, inclusion criteria protocols of amyloidosis. However, incomplete penetrance and high variability of age each clinical trial and our own experience the following criteria have of onset of disease complicates the diagnostic strategy. Thus, regular been developed: screening is required for early identification of the disease. However, the question arises what diagnostic tools should be used for assessment of 1. Stage I to Stage IIIB can be recruited into a clinical trial at any asymptomatic carriers of a TTR gene variant. time. Although endomyocardial biopsy has the highest sensitivity and specificity 2. Stage I non-respondents to Tafamidis after 12 months treatment for detection of cardiac amyloidosis it is not capable for longitudinal who show progression of the disease indicated by. evaluation in asymptomatic carriers. Non-invasive strategies are required • Worsening of ambulation (increase of PND score by one point). to allow frequent testings with time intervals ranging between 6 and • Onset of orthostatic hypotension or impotence. 24 months. ECG, echocardiography, cardiac magnetic resonance imaging, • Progress of cardiomyopathy with worsening of stage of cardiac skeletal scintigraphy, and cardiac biomarkers are potential tools for insufficiency NYHA by 1 point or of cardiac conduction assessment. In general, routine assessment should be based on ECG and disorders. echocardiography. Precise screening of ECG for any abnormalities 3. It is expected than in the short future OLT patients who including conduction disturbances, QRS or T-wave abnormalities is mandatory as abnormal findings are present in almost all patients with underwent illness progression would be enrolled in a clinical trial. cardiac ATTR amyloidosis. Echocardiography assessment should include Conclusions: Disease staging, tafamidis response and OLT limitations are evaluation of diastolic function, longitudinal impairment, as well as speckle the main factors to be considered before recruiting a patient for a clinical tracking. Cardiac
Recommended publications
  • Nuclear Imaging for the Diagnosis of Cardiac Amyloidosis in 2021
    diagnostics Review Nuclear Imaging for the Diagnosis of Cardiac Amyloidosis in 2021 Weijia Li 1,*, Dipan Uppal 1, Yu Chiang Wang 1 , Xiaobo Xu 1, Damianos G. Kokkinidis 2, Mark I. Travin 3 and James M. Tauras 4 1 Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, 1400 Pelham Parkway South, Bronx, NY 10461, USA; [email protected] (D.U.); [email protected] (Y.C.W.); [email protected] (X.X.) 2 Section of Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA; [email protected] 3 Department of Radiology, Division of Nuclear Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA; mtravin@montefiore.org 4 Department of Medicine, Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th Street, Bronx, NY 10467, USA; jtauras@montefiore.org * Correspondence: [email protected] Abstract: Cardiac amyloidosis is caused by the deposition of misfolded protein fibrils into the extracellular space of the heart. The diagnosis of cardiac amyloidosis remains challenging because of the heterogeneous manifestations of the disease. There are many different types of amyloidosis with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis being the most common types of cardiac amyloidosis. Endomyocardial biopsy is considered the gold standard for diagnosing cardiac amyloidosis and differentiating amyloid subtypes, but its use is limited because of the invasive nature of the procedure, with risks for complications and the need for specialized training and centers Citation: Li, W.; Uppal, D.; Wang, to perform the procedure.
    [Show full text]
  • In Vitrocharacterization of Pittsburgh Compound-B Binding to Lewy Bodies
    The Journal of Neuroscience, September 26, 2007 • 27(39):10365–10371 • 10365 Neurobiology of Disease In Vitro Characterization of Pittsburgh Compound-B Binding to Lewy Bodies Michelle T. Fodero-Tavoletti,1,2,4 David P. Smith,1,4 Catriona A. McLean,5 Paul A. Adlard,4 Kevin J. Barnham,1,2,4 Lisa E. Foster,1 Laura Leone,1 Keyla Perez,1,2,4 Mikhalina Corte´s,4 Janetta G. Culvenor,1,3,4 Qiao-Xin Li,1,4 Katrina M. Laughton,1,4 Christopher C. Rowe,6 Colin L. Masters,1,4 Roberto Cappai,1,2,4 and Victor L. Villemagne1,4,6 1Department of Pathology, 2Bio21 Institute, and 3Centre for Neuroscience, The University of Melbourne, Melbourne, Victoria 3010, Australia, 4The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia, 5Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria 3181, Australia, and 6Centre for PET, Austin Hospital, Heidelberg, Victoria 3084, Australia Dementia with Lewy bodies (DLB) is pathologically characterized by the presence of ␣-synuclein-containing Lewy bodies within the neocortical, limbic, and paralimbic regions. Like Alzheimer’s disease (AD), A␤ plaques are also present in most DLB cases. The contri- bution of A␤ to the development of DLB is unclear. [ 11C]-Pittsburgh compound B ([ 11C]-PIB) is a thioflavin-T derivative that has allowed in vivo A␤ burden to be quantified using positron emission tomography (PET). [ 11C]-PIB PET studies have shown similar high cortical [ 11C]-PIB binding in AD and DLB subjects. To establish the potential binding of PIB to ␣-synuclein in DLB patients, we characterized the in vitro binding of PIB to recombinant human ␣-synuclein and DLB brain homogenates.
    [Show full text]
  • Brain Imaging
    Publications · Brochures Brain Imaging A Technologist’s Guide Produced with the kind Support of Editors Fragoso Costa, Pedro (Oldenburg) Santos, Andrea (Lisbon) Vidovič, Borut (Munich) Contributors Arbizu Lostao, Javier Pagani, Marco Barthel, Henryk Payoux, Pierre Boehm, Torsten Pepe, Giovanna Calapaquí-Terán, Adriana Peștean, Claudiu Delgado-Bolton, Roberto Sabri, Osama Garibotto, Valentina Sočan, Aljaž Grmek, Marko Sousa, Eva Hackett, Elizabeth Testanera, Giorgio Hoffmann, Karl Titus Tiepolt, Solveig Law, Ian van de Giessen, Elsmarieke Lucena, Filipa Vaz, Tânia Morbelli, Silvia Werner, Peter Contents Foreword 4 Introduction 5 Andrea Santos, Pedro Fragoso Costa Chapter 1 Anatomy, Physiology and Pathology 6 Elsmarieke van de Giessen, Silvia Morbelli and Pierre Payoux Chapter 2 Tracers for Brain Imaging 12 Aljaz Socan Chapter 3 SPECT and SPECT/CT in Oncological Brain Imaging (*) 26 Elizabeth C. Hackett Chapter 4 Imaging in Oncological Brain Diseases: PET/CT 33 EANM Giorgio Testanera and Giovanna Pepe Chapter 5 Imaging in Neurological and Vascular Brain Diseases (SPECT and SPECT/CT) 54 Filipa Lucena, Eva Sousa and Tânia F. Vaz Chapter 6 Imaging in Neurological and Vascular Brain Diseases (PET/CT) 72 Ian Law, Valentina Garibotto and Marco Pagani Chapter 7 PET/CT in Radiotherapy Planning of Brain Tumours 92 Roberto Delgado-Bolton, Adriana K. Calapaquí-Terán and Javier Arbizu Chapter 8 PET/MRI for Brain Imaging 100 Peter Werner, Torsten Boehm, Solveig Tiepolt, Henryk Barthel, Karl T. Hoffmann and Osama Sabri Chapter 9 Brain Death 110 Marko Grmek Chapter 10 Health Care in Patients with Neurological Disorders 116 Claudiu Peștean Imprint 126 n accordance with the Austrian Eco-Label for printed matters.
    [Show full text]
  • Vizamyl, INN-Flutemetamol (18F)
    26 June 2014 EMA/546752/2014 Committee for Medicinal Products for Human Use (CHMP) Vizamyl flutemetamol (18F) Procedure No. EMEA/H/C/002553 Marketing authorisation holder: GE HEALTHCARE LIMITED Assessment report for an initial marketing authorisation application Assessment report as adopted by the CHMP with all commercially confidential information deleted 30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 5555 Send a question via our website www.ema.europa.eu/contact An agency of the European Union © European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ...................................................................................... 7 1.2. Manufacturers ...................................................................................................... 8 1.3. Steps taken for the assessment of the product ......................................................... 8 2. Scientific discussion ................................................................................ 9 2.1. Introduction......................................................................................................... 9 2.2. Quality aspects .................................................................................................. 11 2.2.1. Introduction ...................................................................................................
    [Show full text]
  • Huidige Situatie En Toekomstverkenning
    Stichting Laka: Documentatie- en onderzoekscentrum kernenergie De Laka-bibliotheek The Laka-library Dit is een pdf van één van de publicaties in This is a PDF from one of the publications de bibliotheek van Stichting Laka, het in from the library of the Laka Foundation; the Amsterdam gevestigde documentatie- en Amsterdam-based documentation and onderzoekscentrum kernenergie. research centre on nuclear energy. Laka heeft een bibliotheek met ongeveer The Laka library consists of about 8,000 8000 boeken (waarvan een gedeelte dus ook books (of which a part is available as PDF), als pdf), duizenden kranten- en tijdschriften- thousands of newspaper clippings, hundreds artikelen, honderden tijdschriftentitels, of magazines, posters, video's and other posters, video’s en ander beeldmateriaal. material. Laka digitaliseert (oude) tijdschriften en Laka digitizes books and magazines from the boeken uit de internationale antikernenergie- international movement against nuclear beweging. power. De catalogus van de Laka-bibliotheek staat The catalogue of the Laka-library can be op onze site. De collectie bevat een grote found at our website. The collection also verzameling gedigitaliseerde tijdschriften uit contains a large number of digitized de Nederlandse antikernenergie-beweging en magazines from the Dutch anti-nuclear power een verzameling video's. movement and a video-section. Laka speelt met oa. haar informatie- Laka plays with, amongst others things, its voorziening een belangrijke rol in de information services, an important role in the Nederlandse anti-kernenergiebeweging. Dutch anti-nuclear movement. Appreciate our work? Feel free to make a small donation. Thank you. www.laka.org | [email protected] | Ketelhuisplein 43, 1054 RD Amsterdam | 020-6168294 | L.P.
    [Show full text]
  • Radiopharmaceuticals and Contrast Media – Oxford Clinical Policy
    UnitedHealthcare® Oxford Clinical Policy Radiopharmaceuticals and Contrast Media Policy Number: RADIOLOGY 034.19 T0 Effective Date: January 1, 2021 Instructions for Use Table of Contents Page Related Policies Coverage Rationale ....................................................................... 1 • Cardiology Procedures Requiring Prior Definitions .................................................................................... 10 Authorization for eviCore Healthcare Arrangement Prior Authorization Requirements .............................................. 10 • Radiation Therapy Procedures Requiring Prior Applicable Codes ........................................................................ 10 Authorization for eviCore Healthcare Arrangement Description of Services ............................................................... 13 • Radiology Procedures Requiring Prior Authorization References ................................................................................... 13 for eviCore Healthcare Arrangement Policy History/Revision Information ........................................... 14 Instructions for Use ..................................................................... 14 Coverage Rationale eviCore healthcare administers claims on behalf of Oxford Health Plans for the following services that may be billed in conjunction with radiopharmaceuticals and/or contrast media: • Radiology Services: Refer to Radiology Procedures Requiring Prior Authorization for eviCore Healthcare Arrangement for additional information.
    [Show full text]
  • Viiith INTERNATIONAL SYMPOSIUM on NUCLEAR MEDICINE
    INIS-mf--10949 VIIIth INTERNATIONAL SYMPOSIUM ON NUCLEAR MEDICINE JUNE 2 - 5, 1986 KARLOVY VARY CZECHOSLOVAKIA ABSTRACTS ABSTRACTS The booklet contains all abstracts of papers submitted in time to the Secretariat of the Symposium. The abstracts were reproduced from the original forms sent by the ithors. The responsibilit >r the contents and gram- matical style the. re lies upon the authors. 17 ANTIBODY GUIDED TUMOR DETECTION IN PATIENTS WITH CARCINOMA. P.Riva.G.Paganelli, C.Cacciaguerra,V.Tison5G.Landi, G. Riceputi,G.Moscatelli.M.Agostini. Istituto Oncologico Romagnolo. Servizio di Medicir.a Nucleare Ospedale M.Bufalini 47023 Cesena ITALY. As a unit of a multicenter clinical trial coordi - nated by the National Reserch Council we studied two groups of patients,in the last three years.In the first group of undred patients affected by ma- lignat melanoma with stage I-IV we were able to de tect the 75% of well documented lesions employing a 99mTC labelled F(ab')2 fragments of MoAb raised a- gainst melanoma (HMW MAA)225.28S(TECNEMAB 1-SORIN BIOMEDICA).In addition a certain number of unknown metastases were also detected and confirmed after- wards. The second group consisted of two-undred pa tients with gastro-intestinal,breast and lung carci^ noma.In these cases we used a 111 In and or 131 I labelled F(ab')i) fragments of a MoAb Raised against CEA(clone F023C5-S'?RIN-Biomedica) with best results in patients bearing colon retto carcinoma and lung cancer.More in detail we obtained the 8<~-% and the 91% of positive scans respectively.In order to im- prove the sensitivity and the tumour/BK ratio some patients with G.I.
    [Show full text]
  • Does Your Patient Have Bile Acid Malabsorption?
    NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #198 NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #198 Carol Rees Parrish, MS, RDN, Series Editor Does Your Patient Have Bile Acid Malabsorption? John K. DiBaise Bile acid malabsorption is a common but underrecognized cause of chronic watery diarrhea, resulting in an incorrect diagnosis in many patients and interfering and delaying proper treatment. In this review, the synthesis, enterohepatic circulation, and function of bile acids are briefly reviewed followed by a discussion of bile acid malabsorption. Diagnostic and treatment options are also provided. INTRODUCTION n 1967, diarrhea caused by bile acids was We will first describe bile acid synthesis and first recognized and described as cholerhetic enterohepatic circulation, followed by a discussion (‘promoting bile secretion by the liver’) of disorders causing bile acid malabsorption I 1 enteropathy. Despite more than 50 years since (BAM) including their diagnosis and treatment. the initial report, bile acid diarrhea remains an underrecognized and underappreciated cause of Bile Acid Synthesis chronic diarrhea. One report found that only 6% Bile acids are produced in the liver as end products of of British gastroenterologists investigate for bile cholesterol metabolism. Bile acid synthesis occurs acid malabsorption (BAM) as part of the first-line by two pathways: the classical (neutral) pathway testing in patients with chronic diarrhea, while 61% via microsomal cholesterol 7α-hydroxylase consider the diagnosis only in selected patients (CYP7A1), or the alternative (acidic) pathway via or not at all.2 As a consequence, many patients mitochondrial sterol 27-hydroxylase (CYP27A1). are diagnosed with other causes of diarrhea or The classical pathway, which is responsible for are considered to have irritable bowel syndrome 90-95% of bile acid synthesis in humans, begins (IBS) or functional diarrhea by exclusion, thereby with 7α-hydroxylation of cholesterol catalyzed interfering with and delaying proper treatment.
    [Show full text]
  • Initial Clinical Comparison of 18F-Florbetapir and 18F-FDG PET in Patients with Alzheimer Disease and Controls
    Journal of Nuclear Medicine, published on May 10, 2012 as doi:10.2967/jnumed.111.099606 Initial Clinical Comparison of 18F-Florbetapir and 18F-FDG PET in Patients with Alzheimer Disease and Controls Andrew B. Newberg1, Steven E. Arnold2, Nancy Wintering1, Barry W. Rovner1, and Abass Alavi2 1Thomas Jefferson University and Hospital, Philadelphia, Pennsylvania; and 2University of Pennsylvania, Philadelphia, Pennsylvania The purpose of this study was to determine how clinical inter- Alzheimer disease (AD) is a brain disorder of older pretations of the 18F-amyloid tracer florbetapir compares diagnos- adults, with symptoms of progressive decline in memory 18 tically with F-FDG PET when evaluating patients with Alzheimer and other cognitive functions. A definitive diagnosis of AD disease (AD) and controls. Methods: Nineteen patients with a clin- ical diagnosis of AD and 21 elderly controls were evaluated with can be established only by demonstrating the presence of both 18F-florbetapir and 18F-FDG PET scans. Scans were inter- abundant senile plaques and neurofibrillary tangles in post- preted together by 2 expert readers masked to any case informa- mortem brain sections (1,2). During life, most patients are tion and were assessed for tracer binding patterns consistent with diagnosed by clinical criteria that imperfectly track with AD. The criteria for interpreting the 18F-florbetapir scan as positive postmortem pathologic findings. The criteria for the diagno- for AD was the presence of binding in the cortical regions relative to sis of AD were defined by the Working Group of the Na- the cerebellum. 18F-FDG PET scans were interpreted as positive if they displayed the classic pattern of hypometabolism in the tem- tional Institute of Neurologic and Communicative Disorders poroparietal regions.
    [Show full text]
  • Molecular Imaging in Alzheimer's Disease
    CORE Metadata, citation and similar papers at core.ac.uk Provided by PubMed Central Nordberg Alzheimer’s Research & Therapy 2011, 3:34 http://alzres.com/content/3/6/34 REVIEW Molecular imaging in Alzheimer’s disease: new perspectives on biomarkers for early diagnosis and drug development Agneta Nordberg* Introduction Abstract Alzheimer’s disease (AD) is characterized by a slow Recent progress in molecular imaging has provided continued deterioration of cognitive processes. Th e fi rst new important knowledge for further understanding symptoms of episodic memory disturbances might be the time course of early pathological disease processes quite subtle. When the patient is assessed for memory in Alzheimer’s disease (AD). Positron emission problems the disease has most probably been ongoing in tomography (PET) amyloid beta (Aβ) tracers such as the brain for several years and has most probably induced Pittsburgh Compound B detect increasing deposition nonrepairable disturbances of important functional of fi brillar Aβ in the brain at the prodromal stages of neuronal networks and loops of the brain. It is a challenge AD, while the levels of fi brillar Aβ appear more stable to test whether some of these changes could be reversed at high levels in clinical AD. There is a need for PET or slowed down with early drug treatment. ligands to visualize smaller forms of Aβ, oligomeric Th e recent progress in AD research has provided new forms, in the brain and to understand how they knowledge for further understanding the pathology interact with synaptic activity and neurodegeneration. processes of AD that precede the onset of clinical disease The infl ammatory markers presently under by many years.
    [Show full text]
  • In Vivo TSPO Signal and Neuroinflammation in Alzheimer's
    cells Review In Vivo TSPO Signal and Neuroinflammation in Alzheimer’s Disease Benjamin B. Tournier 1,2,* , Stergios Tsartsalis 1 , Kelly Ceyzériat 1,3,4 , Valentina Garibotto 3 and Philippe Millet 1,2 1 Division of Adult Psychiatry, Department of Psychiatry, University Hospitals of Geneva, 1205 Geneva, Switzerland; [email protected] (S.T.); [email protected] (K.C.); [email protected] (P.M.) 2 Department of Psychiatry, University of Geneva, 1211 Geneva, Switzerland 3 Division of Nuclear Medicine and Molecular Imaging, Diagnostic Department, Geneva University and Geneva University Hospitals, 1205 Geneva, Switzerland; [email protected] 4 Division of Radiation Oncology, Department of Oncology, University Hospitals of Geneva, 1205 Geneva, Switzerland * Correspondence: [email protected]; Tel.: +41-22-305-5379 Received: 21 July 2020; Accepted: 18 August 2020; Published: 21 August 2020 Abstract: In the last decade, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in in vivo imaging has attempted to demonstrate the presence of neuroinflammatory reactions by measuring the 18 kDa translocator protein (TSPO) expression in many diseases of the central nervous system. We focus on two pathological conditions for which neuropathological studies have shown the presence of neuroinflammation, which translates in opposite in vivo expression of TSPO. Alzheimer’s disease has been the most widely assessed with more than forty preclinical and clinical studies, showing overall that TSPO is upregulated in this condition, despite differences in the topography of this increase, its time-course and the associated cell types. In the case of schizophrenia, a reduction of TSPO has instead been observed, though the evidence remains scarce and contradictory.
    [Show full text]
  • Multicentre Prospective Survey of Sehcat Provision and Practice in the UK
    BMJ Open Gastroenterol: first published as 10.1136/bmjgast-2016-000091 on 1 May 2016. Downloaded from Imaging Multicentre prospective survey of SeHCAT provision and practice in the UK Jennifer A Summers,1,2 Janet Peacock,1,2 Bolaji Coker,1,2 Viktoria McMillan,3,4 Mercy Ofuya,1,2 Cornelius Lewis,3,4 Stephen Keevil,3,5 Robert Logan,6 John McLaughlin,7,8 Fiona Reid,1,2 To cite: Summers JA, ABSTRACT et al Summary box Peacock J, Coker B, . Objective: A clinical diagnosis of bile acid Multicentre prospective malabsorption (BAM) can be confirmed using SeHCAT survey of SeHCAT provision What is already known about this subject? (tauroselcholic (75selenium) acid), a radiolabelled and practice in the UK. BMJ ▸ Bile acid malabsorption (BAM) is an established Open Gastro 2016;3: synthetic bile acid. However, while BAM can be the cause of chronic diarrhoea and results in signifi- e000091. doi:10.1136/ cause of chronic diarrhoea, it is often overlooked as a cantly adverse quality of life for affected individuals. bmjgast-2016-000091 potential diagnosis. Therefore, we investigated the use ▸ Diagnosis of BAM can be confirmed using of SeHCAT for diagnosis of BAM in UK hospitals. SeHCAT (tauroselcholic (75selenium) acid), a Design: A multicentre survey was conducted radiolabelled synthetic bile acid. However, this capturing centre and patient-level information detailing diagnostic tool is not consistently applied in patient care-pathways, clinical history, SeHCAT results, National Health Service (NHS) centres in the UK. Additional material is treatment with bile acid sequestrants (BAS), and ▸ Patients diagnosed with BAM can benefit from published online only.
    [Show full text]