Journal Mobile Options
Table of Contents
Vol. 23, No. 1, 2007
Issue release date: December 2006
Dement Geriatr Cogn Disord 2007;23:55–59
(DOI:10.1159/000096743)

The M694V Variant of the Familial Mediterranean Fever Gene Is Associated with Sporadic Early-Onset Alzheimer’s Disease in an Italian Population Sample

Arra M. · Emanuele E. · Martinelli V. · Minoretti P. · Bertona M. · Geroldi D.
aInterdepartmental Center for Research in Molecular Medicine and bSection of Psychiatry, Department of Health Sciences, University of Pavia, Pavia, Italy

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Background: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer’s disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. Methods: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. Results: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24–6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34–1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). Conclusion: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.



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. St George-Hyslop PH, Petit A: Molecular biology and genetics of Alzheimer’s disease. C R Biol 2005;328:119–130.
  2. Imbimbo BP, Lombard J, Pomara N: Pathophysiology of Alzheimer’s disease. Neuroimaging Clin North Am 2005;15:727–753.
  3. Heese K, Akatsu H: Alzheimer’s disease – An interactive perspective. Curr Alzheimer Res 2006;3:109–121.
  4. Mahley RW, Weisgraber KH, Huang Y: Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer’s disease. Proc Natl Acad Sci USA 2006;103:5644–5651.
  5. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA: Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993;261:921–923.
  6. Khachaturian AS, Corcoran CD, Mayer LS, Zandi PP, Breitner JC, Cache County Study Investigators: Apolipoprotein E epsilon4 count affects age at onset of Alzheimer disease, but not lifetime susceptibility: The Cache County Study. Arch Gen Psychiatry 2004;61:518–524.
  7. Mooser V, Helbecque N, Miklossy J, Marcovina SM, Nicod P, Amouyel P: Interactions between apolipoprotein E and apolipoprotein(a) in patients with late-onset Alzheimer disease. Ann Intern Med 2000;132:533–537.
  8. Emanuele E, Peros E, Tomaino C, Feudatari E, Bernardi L, Binetti G, Maletta R, D’Angelo A, Montagna L, Bruni AC, Geroldi D: Apolipoprotein(a) null phenotype is related to a delayed age at onset of Alzheimer’s disease. Neurosci Lett 2004;357:45–48.
  9. Hull M, Lieb K, Fiebich BL: Pathways of inflammatory activation in Alzheimer’s disease: potential targets for disease modifying drugs. Curr Med Chem 2002;9:83–88.
  10. Walsh S, Aisen PS: Inflammatory processes and Alzheimer’s disease. Expert Rev Neurother 2004;4:793–798.
  11. Aisen PS: Inflammation and Alzheimer disease. Mol Chem Neuropathol 1996;28:83–88.
  12. Schaner PE, Gumucio DL: Familial Mediterranean fever in the post-genomic era: how an ancient disease is providing new insights into inflammatory pathways. Curr Drug Targets Inflamm Allergy 2005;4:67–76.
  13. Onen F: Familial Mediterranean fever. Rheumatol Int 2006;26:489–496.
  14. Mott RT, Hulette CM: Neuropathology of Alzheimer’s disease. Neuroimag Clin North Am 2005;15:755–765.
  15. Fidder H, Chowers Y, Ackerman Z, Pollak RD, Crusius JB, Livneh A, Bar-Meir S, Avidan B, Shinhar Y: The familial Mediterranean fever (MEVF) gene as a modifier of Crohn’s disease. Am J Gastroenterol 2005;100:338–343.
  16. Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y: Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 2005;64:1009–1014.
  17. Grimaldi MP, Candore G, Vasto S, Caruso M, Caimi G, Hoffmann E, Colonna-Romano G, Lio D, Shinar Y, Franceschi C, Caruso C: Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population. J Leukoc Biol 2006;79:611–615.
  18. Minoretti P, Gazzaruso C, Vito CD, Emanuele E, Bianchi M, Coen E, Reino M, Geroldi D: Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer’s disease. Neurosci Lett 2006;391:147–149.
  19. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 1984;34:939–944.
  20. Geroldi D, Minoretti P, Bianchi M, Di Vito C, Reino M, Bertona M, Emanuele E: Genetic association of α2-Heremans-Schmid glycoprotein polymorphism with late-onset Alzheimer’s disease in Italians. Neurosci Lett 2005;386:176–178.
  21. Milledge J, Shaw PJ, Mansour A, Williamson S, Bennetts B, Roscioli T, Curtin J, Christodoulou J: Allogeneic bone marrow transplantation: cure for familial Mediterranean fever. Blood 2002;100:774–777.
  22. Hixson JE, Vernier DT: Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990;31:545–548.
  23. Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES: The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem 2002;277:21119–21122.
  24. Chae JJ, Komarow HD, Cheng J, Wood G, Raben N, Liu PP, Kastner DL: Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol Cell 2003;11:591–604.
  25. Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, Casadei V, Grimaldi LM: Increased plasma levels of interleukin-1, interleukin-6 and α1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals from the brain? J Neuroimmunol 2000;103:97–102.
  26. Griffin WS, Mrak RE: Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer’s disease. J Leukoc Biol 2002;72:233–238.
  27. Sciacca FL, Ferri C, Licastro F, Veglia F, Biunno I, Gavazzi A, Calabrese E, Martinelli Boneschi F, Sorbi S, Mariani C, Franceschi M, Grimaldi LM: Interleukin-1β polymorphism is associated with age at onset of Alzheimer’s disease. Neurobiol Aging 2003;24:927–931.
  28. de la Torre JC: Alzheimer disease as a vascular disorder: nosological evidence. Stroke 2002;33:1152–1162.
  29. de la Torre JC: Alzheimer’s disease is a vasocognopathy: a new term to describe its nature. Neurol Res 2004;26:517–524.
  30. Holmans P, Hamshere M, Hollingworth P, Rice F, Tunstall N, Jones S, Moore P, Wavrant DeVrieze F, Myers A, Crook R, Compton D, Marshall H, Meyer D, Shears S, Booth J, Ramic D, Williams N, Norton N, Abraham R, Kehoe P, Williams H, Rudrasingham V, O’Donovan M, Jones L, Hardy J, Goate A, Lovestone S, Owen M, Williams J: Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 2005;135:24–32.
  31. Li YJ, Scott WK, Hedges DJ, Zhang F, Gaskell PC, Nance MA, Watts RL, Hubble JP, Koller WC, Pahwa R, Stern MB, Hiner BC, Jankovic J, Allen FA Jr, Goetz CG, Mastaglia F, Stajich JM, Gibson RA, Middleton LT, Saunders AM, Scott BL, Small GW, Nicodemus KK, Reed AD, Schmechel DE, Welsh-Bohmer KA, Conneally PM, Roses AD, Gilbert JR, Vance JM, Haines JL, Pericak-Vance MA: Age at onset in two common neurodegenerative diseases is genetically controlled. Am J Hum Genet 2002;70:985–993.
  32. Lio D, Annoni G, Licastro F, Crivello A, Forte GI, Scola L, Colonna-Romano G, Candore G, Arosio B, Galimberti L, Vergani C, Caruso C: Tumor necrosis factor α –308A/G polymorphism is associated with age at onset of Alzheimer’s disease. Mech Ageing Dev 2006;127:567–571.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50