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Research and Clinical Interests

Dr. Frangione is studying the relationship between protein misfolding (amyloid) and Alzheimer's disease and the mechanisms leading to dementia and/or stroke. His current lines of investigation include 1) the search for mutations in familial Alzheimer disease and non-Aβ amyloidosis; 2) their mechanism of protein aggregation and neuronal cell death; 3) the development of transgenic animals for therapeutic approaches and 4) the relation between chaperones (e.g. ApoE, J, etc) and amyloidogenesis.

Selected Publications

Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S, MastersCL, Merlini G, Saraiva MJ, Sipe JD. A primer of amyloid nomenclature. Amyloid. 2007 Sep;14(3):179-83. Cited in Pubmed; PMID 17701465.

Lashley T, Holton JL, Verbeek MM, Rostagno A, Bojsen-Møller M, David G, van Horssen J, Braendgaard H, Plant G, Frangione B, Ghiso J, Revesz T. Molecular chaperons, amyloid and preamyloid lesions in the BRI2 gene-related dementias: a morphological study. Neuropathol Appl Neurobiol. 2006 Oct;32(5):492-504. Cited in Pubmed; PMID 16972883.

Leal MC, Dorfman VB, Gamba AF, Frangione B, Wisniewski T, Castaño EM, Sigurdsson EM, Morelli L. Plaque-associated overexpression of insulin-degrading enzyme in the cerebral cortex of aged transgenic tg2576 mice with Alzheimer pathology. J Neuropathol Exp Neurol. 2006 Oct;65(10):976-87. Cited in Pubmed; PMID 17021402.

Ghiso J, Rostagno A, Tomidokoro Y, Lashley T, Bojsen-Møller M, Braendgaard H, Plant G, Holton J, Lal R, Revesz T, Frangione B. Genetic alterations of the BRI2 gene: familial British and Danish dementias. Brain Pathol. 2006 Jan;16(1):71-9. Cited in Pubmed; PMID 16612984.

Tomidokoro Y, Lashley T, Rostagno A, Neubert TA, Bojsen-Møller M, Braendgaard H, Plant G, Holton J, Frangione B, Révész T, Ghiso J. Familial Danish dementia: co-existence of Danish and Alzheimer amyloid subunits (ADan and Aβ) in the absence of compact plaques. J Biol Chem. 2005 Nov 4;280(44):36883-94. Epub 2005 Aug 9. Cited in Pubmed; PMID 16091362.

Rábano A, Jiménez-Huete A, Acevedo B, Calero M, Ghiso J, Valdés I, Gavilondo J, Frangione B, Méndez E. Diversity of senile plaques in Alzheimer's disease as revealed by a new monoclonal antibody that recognizes an internal sequence of the Abeta peptide. Curr Alzheimer Res. 2005 Oct;2(4):409-17. Cited in Pubmed; PMID 16248846.

Fotinopoulou A, Tsachaki M, Vlavaki M, Poulopoulos A, Rostagno A, Frangione B, Ghiso J, Efthimiopoulos S. BRI2 interacts with amyloid precursor protein (APP) and regulates amyloid beta (Aβ) production. J Biol Chem. 2005 Sep 2;280(35):30768-72. Epub 2005 Jul 18. Cited in Pubmed; PMID 16027166.

Matsuda S, Giliberto L, Matsuda Y, Davies P, McGowan E, Pickford F, Ghiso J, Frangione B, D'Adamio L. The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production. J Biol Chem. 2005 Aug 12;280(32):28912-6. Epub 2005 Jun 27. Cited in Pubmed; PMID 15983050.

Rostagno A, Tomidokoro Y, Lashley T, Ng D, Plant G, Holton J, Frangione B, Revesz T, Ghiso J. Chromosome 13 dementias. Cell Mol Life Sci. 2005 Aug;62(16):1814–25. Cited in Pubmed; PMID 15968464.

Quist A, Doudevski I, Lin H, Azimova R, Ng D, Frangione B, Kagan B, Ghiso J, Lal R. Amyloid ion channels: a common structural link for protein-misfolding disease. Proc Natl Acad Sci U S A. 2005 Jul 26;1 02(30):10427-32. Cited in Pubmed; PMID 16020533.

Morelli L, Llovera RE, Alonso LG, Frangione B, de Prat-Gay G, Ghiso J, Castaño EM. Insulin-degrading enzyme degrades amyloid peptides associated with British and Danish familial dementia. Biochem Biophys Res Commun. 2005 Jul 8;332(3):808-16. Cited in Pubmed; PMID 15913558.

Morelli L, Llovera RE, Mathov I, Lue LF, Frangione B, Ghiso J, Castaño EM. Insulin-degrading enzyme in brain microvessels: proteolysis of amyloid {beta} vasculotropic variants and reduced activity in cerebral amyloid angiopathy. J Biol Chem. 2004 Dec 31;279(53):56004-13. Epub 2004 Oct 15. Cited in Pubmed; PMID 15489232.

Ghiso J, Shayo M, Calero M, Ng D, Tomidokoro Y, Gandy S, Rostagno A, Frangione B. Systemic catabolism of Alzheimer's Abeta40 and Abeta42. J Biol Chem. 2004 Oct 29;279(44):45897-908. Epub 2004 Aug 20. Cited in Pubmed; PMID 15322125.

Zanusso G, Farinazzo A, Prelli F, Fiorini M, Gelati M, Ferrari S, Righetti PG,. Identification of distinct N-terminal truncated forms of prion protein in different Creutzfeldt-Jakob disease subtypes. J Biol Chem. 2004 Sep 10;279(37):38936-42. Epub 2004 Jul 9. Cited in Pubmed; PMID 15247220.

Sastre M, Calero M, Pawlik M, Mathews PM, Kumar A, Danilov V, Schmidt SD, Nixon RA, Frangione B, Levy E. Binding of cystatin C to Alzheimer's amyloid beta inhibits in vitro amyloid fibril formation. Neurobiol Aging. 2004 Sep;25(8):1033-43. Cited in Pubmed; PMID 15212828.

Selected Books and Reviews

Cam J, Meyerson JL, Frangione B, Ghiso J, Rostagno A. Oligomeric assemblies of the Aβ dutch mutant induce the formation of nucleosomes in primary cerebral endothelial cells. In: Iqbal K, Winblad B, Avila J, editors. Alzheimer’s Disease: New Advances. Bologna, Italy: Medimond International Proceedings; 2007. pp. 397–402.

Frangione B, Ghiso J. Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type – The role of amyloid in dementia and stroke. In: Jucker M, Beyreuther K, Haass C, Nitsch RM, Christen Y, editors. Alzheimer: 100 years and beyond. Berlin, Heidelberg: Springer-Verlag; 2006. pp. 242-6.

Levy E, Prelli F, Frangione B. Studies on the first described Alzheimer's disease amyloid beta mutant the Dutch variant [review]. J Alzheimers Dis. 2006;9:329-39.

Ghiso J, Rostagno A, Tomidokoro Y, Lashley T, Holton JL, Plant G, Revesz T, Frangione B. Familial British and Danish Dementias. Vol. 2. In: Sipe JD, editor. Amyloid Proteins: The β-Sheet Conformation and Disease. Weinheim: Wiley-VCH Verlag; 2005. pp. 515-26.

Calero M, Rostagno A, Frangione B, Ghiso J. Clusterin and Alzheimer’s disease. In: Harris R, editor. Subcellular Biochemistry: Alzheimer’s Disease. Vol 38. Berlin: Plenum Press / Kluwer; 2005. pp. 273-98.

Wisniewski T, Frangione B. Immunological and anti-chaperone therapeutic approaches for Alzheimer disease. Brain Pathol. 2005 Jan;15(1):72–7. Cited in Pubmed; PMID 15779239.

Sigurdsson EM, Wisniewski T, Frangione B. A Safer Vaccines for Alzheimer’s and Prion Diseases? In: Iqbal K, Winblad B, editors. Alzheimer’s Disease and Related Disorders: Research Advances. Bucharest, Romania: Ana Asian Intl. Acad. Of Aging; 2003. pp. 533-40.

Révész T, Ghiso J, Holton J, Frangione B. Inherited amyloidoses and neurodegeneration: familial British dementia and familial Danish dementia. In: Dickson D, editor. Neurodegeneration: The molecular pathology of dementia and movements disorders. Basel, Switzerland: International Society of Neuropathology; 2003. pp. 380-5.

Frangione B, Prelli F, Ghiso J, Revesz T. Familial and Sporadic Cerebral Amyloid Angiopathies. In: Korczyn AD, editor. Third International Congress On Vascular Dementia: Prague (Czech Republic) October 23-26, 2003. Bologna: Monduzzi editore, International Proceedings Division; 2003. pp. 35-46.

Sigurdsson EM, Wisniewski T, Frangione B. A safer vaccine for Alzheimer's disease? Neurobiol Aging. 2002;23:1001-8.

Ghiso J, Frangione B. Amyloidosis and Alzheimer’s disease. Advanced Drug Discovery Reviews. 2002;54:1539-51.

Revesz T, Ghiso J, Lashley T, Plant G, Rostagno A, Frangione B, Holton J. Cerebral Amyloid Angiopathies: A Pathologic, Biochemical and Genetic View. J Neuropath Exp Neurol. 2003;62:885-98.

Matsubara E, Shoji M, Murakami T, Abe K, Frangione B, Ghiso J. Platelet Microparticles as Carrier of Soluble Alzheimer’s Amyloid β (sAβ). Alzheimer’s Disease: Vascular Etiology and Pathology. Annals of the New York Academy of Sciences. Vol. 977. 2002 Nov;340-8.

Matsubara E, Shoji M, Murakami T, Abe K, Frangione B, Ghiso J. Vascular Amyloidosis in Neurodegenerative Conditions. Drug News & Perspectives. 2002;15:439-44.

Organizational Associations

American Association of Immunologists; British Society for Immunology; American Federation for Clinical Research; American Society for Clinical Investigation; American College of Rheumatology; American Society for Biochemistry and Molecular Biology; American Association of Neuropathologists; Society for Neuroscience; The Henry Kunkel Society; Cambridge Society, England.

Selected Awards

1966-1969 Special Fellow, The Arthritis Foundation, New York, New York
1989 MERIT Award, National Institutes of Health, "Structure of Immunoglobulins and Related Proteins" (AR 02594)
1992 Leadership and Excellence in Alzheimer's Disease (L.E.A.D.) Award, National Institutes of Health, "Alzheimer's Disease and Amyloid Proteins" (AG10953)
1993 Potamkin Prize for Alzheimer's Disease Research, Annual Award of the American Academy of Neurology
1994 The Metropolitan Life Foundation Award for Medical Research
1997 MERIT Award, National Institutes of Health, "Amyloidosis and Alzheimer's Disease" (AG 05891)
1999 Member of the Argentinian National Academy of Medicine
1999 Doctor of Science, Honoris Causa, University of Buenos Aires, Buenos Aires, Argentina
2000 Lifetime Achievement Award, VII International Congress of Alzheimer's Disease