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Vol. 16, No. 1, 2008
Issue release date: December 2007
Section title: Paper
Free Access
Neurosignals 2008;16:19–23
(DOI:10.1159/000109755)

PENN Biomarker Core of the Alzheimer’s Disease Neuroimaging Initiative

Shaw L.M.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA
email Corresponding Author

Abstract

There is a pressing need to develop effective prevention and disease-modifying treatments for Alzheimer’s disease (AD), a dreaded affliction whose incidence increases almost logarithmically with age starting at about 65 years. A key need in the field of AD research is the validation of imaging and biochemical biomarkers. Biomarker tests that are shown to reliably predict the disease before it is clinically expressed would permit testing of new therapeutics at the earliest time point possible in order to give the best chance for delaying the onset of dementia in these patients. In this review the current state of AD biochemical biomarker research is discussed. A new set of guidelines for the diagnosis of AD in the research setting places emphasis on the inclusion of selected imaging and biochemical biomarkers, in addition to neuropsychological behavioral testing. Importantly, the revised guidelines were developed to identify patients at the earliest stages prior to full-blown dementia as well as patients with the full spectrum of the disease. The Alzheimer’s Disease Neuroimaging Initiative is a multicenter consortium study that includes as one of its primary goals the development of standardized neuroimaging and biochemical biomarker methods for AD clinical trials, as well as using these to measure changes over time in mildly cognitively impaired patients who convert to AD as compared to the natural variability of these in control subjects and their further change over time in AD patients. Validation of the biomarker results by correlation analyses with neuropsychological and neurobehavioral test data is one of the primary outcomes of this study. This validation data will hopefully provide biomarker test performance needed for effective measurement of the efficacy of new treatment and prevention therapeutic agents.

© 2008 S. Karger AG, Basel


  

Key Words

  • Alzheimer’s disease
  • Alzheimer’s Disease Neuroimaging Initiative
  • Biomarkers

References

  1. Heberty LE, Scherr PA, Bienias JL, et al: Alzheimer disease in the US population. Arch Neurol 2003;1119–1122.

    External Resources

  2. Alzheimer’s Association: Fact Sheet, Alzheimer’s Disease. www.alz.org.
  3. Forman MS, Trojanowski JQ, Lee VM-Y: Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004;10:1055–1063.
  4. Selkoe DJ: Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 2004;6:1054–1061.
  5. Skovronsky DM, Lee VM-Y, Trojanowski JQ: Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol Mech Dis 2006;1:151–170.
  6. Forman MS, Farmer J, Johnson JK, et al: Frontotemporal dementia: clinicopathological correlations. Ann Neurol 2006;59:952–962.
  7. Forman MS, Lee VM-Y, Trojanowski JQ: Nosology of Parkinson’s disease: looking for the way out of a quackmire. Neuron 2005;47:479–482.
  8. Savitt JM, Dawson VL, Dawson TM: Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 2006;116:1744–1754.
  9. McKeith IG, Dickson DW, Lowe J, et al: Dementia with Lewy bodies: diagnosis and management: third report of the DLB Consortium. Neurology 2005;65:1863–1872.
  10. Shaw LM, Korecka M, Clark CM, Lee VM-Y, Trojanowski JQ: Biomarkers of neurodegeneration for diagnosing and monitoring therapeutics. Nat Rev Drug Discov 2007;6:295–303.
  11. Blennow K, Hampel H: CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2003;2:605–613.
  12. Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, et al: Decreased β-amyloid1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 2003;289:2094–2103.
  13. Hannson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L: Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228–234.
  14. Consensus report of the Working Group on: ‘Biological Markers of Alzheimer’s Disease’. The Ronald and Nancy Reagen Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group. Neurobiol Aging 1998;19:109–116.
  15. Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, et al: Biological markers for therapeutic trials in Alzheimer’s disease – proceedings of the Biological Measures Working Group: NIA Initiative on Neuroimaging in Alzheimer’s Disease. Neurobiol Aging 2003;24:521–536.
  16. Thal LJ, Kantarci K, Reiman EM, et al: The role of biomarkers in clinical trials for Alzheimer’s disease. Alzheimer Dis Assoc Disord 2006;20:6–15.
  17. Clarke R, Smith D, Jobst DM, Refsum H: Folate, vitamin B12 and serum homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449–1455.
  18. Seshadri S, Beiser A, Selhub J, et al: Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–483.
  19. Hsiung G-YR, Sadovnick AD, Feldman H: Apolipoprotein E ε4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging. Can Med Assoc 2004;171:863–867.
  20. Dubois R, Feldman HH, Jacova C, DeKosky ST, Barberger-Gateau P, et al: Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734–746.

  

Author Contacts

Leslie M. Shaw, PhD
Department of Pathology and Laboratory Medicine
7 Founders Pavilion, 3400 Spruce Street
Philadelphia, PA 19104 (USA)
Tel. +1 215 662 6575, Fax +1 215 662 7529, E-Mail shawlmj@mail.med.upenn.edu

  

Article Information

Published online: December 5, 2007
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 0, Number of References : 20

  

Publication Details

Neurosignals

Vol. 16, No. 1, Year 2008 (Cover Date: December 2007)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (print), 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

There is a pressing need to develop effective prevention and disease-modifying treatments for Alzheimer’s disease (AD), a dreaded affliction whose incidence increases almost logarithmically with age starting at about 65 years. A key need in the field of AD research is the validation of imaging and biochemical biomarkers. Biomarker tests that are shown to reliably predict the disease before it is clinically expressed would permit testing of new therapeutics at the earliest time point possible in order to give the best chance for delaying the onset of dementia in these patients. In this review the current state of AD biochemical biomarker research is discussed. A new set of guidelines for the diagnosis of AD in the research setting places emphasis on the inclusion of selected imaging and biochemical biomarkers, in addition to neuropsychological behavioral testing. Importantly, the revised guidelines were developed to identify patients at the earliest stages prior to full-blown dementia as well as patients with the full spectrum of the disease. The Alzheimer’s Disease Neuroimaging Initiative is a multicenter consortium study that includes as one of its primary goals the development of standardized neuroimaging and biochemical biomarker methods for AD clinical trials, as well as using these to measure changes over time in mildly cognitively impaired patients who convert to AD as compared to the natural variability of these in control subjects and their further change over time in AD patients. Validation of the biomarker results by correlation analyses with neuropsychological and neurobehavioral test data is one of the primary outcomes of this study. This validation data will hopefully provide biomarker test performance needed for effective measurement of the efficacy of new treatment and prevention therapeutic agents.

© 2008 S. Karger AG, Basel


  

Author Contacts

Leslie M. Shaw, PhD
Department of Pathology and Laboratory Medicine
7 Founders Pavilion, 3400 Spruce Street
Philadelphia, PA 19104 (USA)
Tel. +1 215 662 6575, Fax +1 215 662 7529, E-Mail shawlmj@mail.med.upenn.edu

  

Article Information

Published online: December 5, 2007
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 0, Number of References : 20

  

Publication Details

Neurosignals

Vol. 16, No. 1, Year 2008 (Cover Date: December 2007)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424–862X (print), 1424–8638 (Online)

For additional information: http://www.karger.com/NSG


Article / Publication Details

First-Page Preview
Abstract of Paper

Published online: 12/5/2007
Issue release date: December 2007

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 0

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Heberty LE, Scherr PA, Bienias JL, et al: Alzheimer disease in the US population. Arch Neurol 2003;1119–1122.

    External Resources

  2. Alzheimer’s Association: Fact Sheet, Alzheimer’s Disease. www.alz.org.
  3. Forman MS, Trojanowski JQ, Lee VM-Y: Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004;10:1055–1063.
  4. Selkoe DJ: Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 2004;6:1054–1061.
  5. Skovronsky DM, Lee VM-Y, Trojanowski JQ: Neurodegenerative diseases: new concepts of pathogenesis and their therapeutic implications. Annu Rev Pathol Mech Dis 2006;1:151–170.
  6. Forman MS, Farmer J, Johnson JK, et al: Frontotemporal dementia: clinicopathological correlations. Ann Neurol 2006;59:952–962.
  7. Forman MS, Lee VM-Y, Trojanowski JQ: Nosology of Parkinson’s disease: looking for the way out of a quackmire. Neuron 2005;47:479–482.
  8. Savitt JM, Dawson VL, Dawson TM: Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 2006;116:1744–1754.
  9. McKeith IG, Dickson DW, Lowe J, et al: Dementia with Lewy bodies: diagnosis and management: third report of the DLB Consortium. Neurology 2005;65:1863–1872.
  10. Shaw LM, Korecka M, Clark CM, Lee VM-Y, Trojanowski JQ: Biomarkers of neurodegeneration for diagnosing and monitoring therapeutics. Nat Rev Drug Discov 2007;6:295–303.
  11. Blennow K, Hampel H: CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2003;2:605–613.
  12. Sunderland T, Linker G, Mirza N, Putnam KT, Friedman DL, Kimmel LH, et al: Decreased β-amyloid1–42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 2003;289:2094–2103.
  13. Hannson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L: Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 2006;5:228–234.
  14. Consensus report of the Working Group on: ‘Biological Markers of Alzheimer’s Disease’. The Ronald and Nancy Reagen Research Institute of the Alzheimer’s Association and the National Institute on Aging Working Group. Neurobiol Aging 1998;19:109–116.
  15. Frank RA, Galasko D, Hampel H, Hardy J, de Leon MJ, et al: Biological markers for therapeutic trials in Alzheimer’s disease – proceedings of the Biological Measures Working Group: NIA Initiative on Neuroimaging in Alzheimer’s Disease. Neurobiol Aging 2003;24:521–536.
  16. Thal LJ, Kantarci K, Reiman EM, et al: The role of biomarkers in clinical trials for Alzheimer’s disease. Alzheimer Dis Assoc Disord 2006;20:6–15.
  17. Clarke R, Smith D, Jobst DM, Refsum H: Folate, vitamin B12 and serum homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449–1455.
  18. Seshadri S, Beiser A, Selhub J, et al: Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–483.
  19. Hsiung G-YR, Sadovnick AD, Feldman H: Apolipoprotein E ε4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging. Can Med Assoc 2004;171:863–867.
  20. Dubois R, Feldman HH, Jacova C, DeKosky ST, Barberger-Gateau P, et al: Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734–746.