Vincent Marchesi, MD, PhD
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Research Summary
During the past decade my interest have focused on the pathogenesis of Alzheimer's disease, one of the most destructive neurological diseases that affects millions worldwide. This insidious disease becomes clinically symptomatic during the sixth decade of life, but there are reasons for believing that the disease process may begin one or two decades earlier, and abnormal metabolism of amyloid abeta peptides may be an important contributing factor.
I have been analyzing naturally occurring auto-antibodies to the amyloid abeta protein as a measure of the body's response to either elevated levels or abnormal forms of these peptides. It is my feeling that the development of a reliable way to identify individuals who are risk for AD before the disease is evident is a critical unmet need. This lack of early detection hampers our ability to develop new therapies.
Specialized Terms: Pathogenesis of Alzheimer's disease; Neurodegeneration; Amyloid abeta metabolism; Auto-antibodies; Protein-folding
Extensive Research Description
Two recent reports present evidence that naturally occurring auto-antibodies to abeta might be neuro-protective. In one study auto-antibodies to an aggregated form of abeta were found to be depressed in AD patients, but, paradoxically, elevated in normal, young adults. A second report describes a decrease in the incidence of AD in people treated with intravenous immunoglobulin preparations Both results are consistent with the idea that natural antibodies to abeta exist in all people and are depleted in advanced AD.
Contrary to these results, we have found that there is no clear correlation with levels of anti-abeta antibodies and the clinical status of the donor. Antibodies to a peptide fragment (p16-34) of abeta are elevated in many but not all individuals with advanced AD. We have found that intravenous immunoglobulin preparations also react with the p16-34 abeta fragment. If naturally occurring antibodies to abeta are indeed neuro-protective, as the available evidence suggests, it will be important to determine which epitopes of abeta induce the protective response, and, equally important, to identify the epitopes that might confer toxicity. The patho-physiological significance of auto-antibodies to amyloid abeta peptides is clearly a complicated question that deserves further study. auto-antibodies to amyloid abeta peptides
neuro-protective antibodies
Research Interests
Alzheimer Disease; Autoantibodies; Cell Biology; Pathology; Protein Folding
Selected Publications
- The Relevance of Research on Red Cell Membranes to the Understanding of Complex Human Disease: A Personal PerspectiveMarchesi VT. The Relevance of Research on Red Cell Membranes to the Understanding of Complex Human Disease: A Personal Perspective. Annual Review Of Pathology Mechanisms Of Disease 2008, 3: 1-9. PMID: 18039128, DOI: 10.1146/annurev.pathmechdis.3.121806.154321.
- An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's diseaseMarchesi VT. An alternative interpretation of the amyloid Aβ hypothesis with regard to the pathogenesis of Alzheimer's disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 9093-9098. PMID: 15967987, PMCID: PMC1166615, DOI: 10.1073/pnas.0503181102.
- www.fasebj.orgMarchesi V. www.fasebj.org. The FASEB Journal 1998, 12: 1253-1253. PMID: 9761769, DOI: 10.1096/fasebj.12.13.1253.
- From Molecular Analysis to Medical Practice: Recent Studies Reveal New Therapeutic Targets for an Old MedicineMarchesi V. From Molecular Analysis to Medical Practice: Recent Studies Reveal New Therapeutic Targets for an Old Medicine. The FASEB Journal 1998, 12: 1061-1061. PMID: 9737709, DOI: 10.1096/fasebj.12.12.1061.
- Hard Days … on the Endless Frontier? … or in the Trenches?Marchesi V. Hard Days … on the Endless Frontier? … or in the Trenches? The FASEB Journal 1998, 12: 253-253. PMID: 9506464, DOI: 10.1096/fasebj.12.3.253.
- “According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non‐author.”Marchesi V. “According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non‐author.”. The FASEB Journal 1998, 12: 1-1. DOI: 10.1096/fsb2fasebj.12.1.1.
- “According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non-author.”Marchesi V. “According to the definition of intellectual property,” Mario Biagioli notes, “a scientist is literally a non-author.”. The FASEB Journal 1998, 12: 1-1. DOI: 10.1096/fasebj.12.1.1.
- The Life Sciences Forum–A Call for ContributionsMarchesi V. The Life Sciences Forum–A Call for Contributions. The FASEB Journal 1996, 10: 1111-1111. PMID: 8751712, DOI: 10.1096/fasebj.10.10.8751712.
- Yale’s Boyer Center for Molecular MedicineMarchesi V. Yale’s Boyer Center for Molecular Medicine. Molecular Medicine 1995, 1: 477-478. PMID: 8529113, PMCID: PMC2229965, DOI: 10.1007/bf03401584.
- In vitro assembly of multiprotein complexes containing alpha, beta, and gamma tubulin, heat shock protein HSP70, and elongation factor 1 alpha.Marchesi V, Ngo N. In vitro assembly of multiprotein complexes containing alpha, beta, and gamma tubulin, heat shock protein HSP70, and elongation factor 1 alpha. Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90: 3028-3032. PMID: 8464918, PMCID: PMC46230, DOI: 10.1073/pnas.90.7.3028.
- Interaction of platelet protein 4.1 with the cytoskeleton of activated plateletsHorne W, Golish C, Marchesi V. Interaction of platelet protein 4.1 with the cytoskeleton of activated platelets. Journal Of Molecular And Cellular Cardiology 1987, 19: s15. DOI: 10.1016/s0022-2828(87)80668-5.
- Stabilizing Infrastructure of Cell MembranesMarchesi V. Stabilizing Infrastructure of Cell Membranes. Annual Review Of Cell And Developmental Biology 1985, 1: 531-561. PMID: 3916322, DOI: 10.1146/annurev.cb.01.110185.002531.
- Vimentin Binds to the Human RBC Membrane and Associates with AnkyrinGEORGATOS S, WEAVER D, MARCHESI V. Vimentin Binds to the Human RBC Membrane and Associates with Ankyrin. Annals Of The New York Academy Of Sciences 1985, 455: 691-693. DOI: 10.1111/j.1749-6632.1985.tb50446.x.
- The binding of vimentin to human erythrocyte membranes: a model system for the study of intermediate filament-membrane interactions.Georgatos S, Marchesi V. The binding of vimentin to human erythrocyte membranes: a model system for the study of intermediate filament-membrane interactions. Journal Of Cell Biology 1985, 100: 1955-1961. PMID: 3158664, PMCID: PMC2113610, DOI: 10.1083/jcb.100.6.1955.
- Site specificity in vimentin-membrane interactions: intermediate filament subunits associate with the plasma membrane via their head domains.Georgatos S, Weaver D, Marchesi V. Site specificity in vimentin-membrane interactions: intermediate filament subunits associate with the plasma membrane via their head domains. Journal Of Cell Biology 1985, 100: 1962-1967. PMID: 3158665, PMCID: PMC2113597, DOI: 10.1083/jcb.100.6.1962.
- Isolation of spectrin subunits and reassociation in vitro. Analysis by fluorescence polarization.Yoshino H, Marchesi V. Isolation of spectrin subunits and reassociation in vitro. Analysis by fluorescence polarization. Journal Of Biological Chemistry 1984, 259: 4496-4500. PMID: 6707015, DOI: 10.1016/s0021-9258(17)43074-2.
- Structure and function of the erythrocyte membrane skeleton.Marchesi V. Structure and function of the erythrocyte membrane skeleton. Progress In Clinical And Biological Research 1984, 159: 1-12. PMID: 6236465.
- The red cell membrane skeleton: recent progress.Marchesi V. The red cell membrane skeleton: recent progress. Blood 1983, 61: 1-11. PMID: 6293625, DOI: 10.1182/blood.v61.1.1.bloodjournal6111.
- The membrane skeleton as a potential target for toxic agents.Marchesi V. The membrane skeleton as a potential target for toxic agents. Mead Johnson Symposium On Perinatal And Developmental Medicine 1982, 13-6. PMID: 6765455.
- Immunobiology of the Erythrocyte . S. Gerald Sandler , Jacob Nusbacher , Moses S. SchanfieldMarchesi V. Immunobiology of the Erythrocyte . S. Gerald Sandler , Jacob Nusbacher , Moses S. Schanfield. The Quarterly Review Of Biology 1981, 56: 520-520. DOI: 10.1086/412562.
- The carboxyl-terminal domain of human erythrocyte band 3. Description, isolation, and location in the bilayer.Markowitz S, Marchesi V. The carboxyl-terminal domain of human erythrocyte band 3. Description, isolation, and location in the bilayer. Journal Of Biological Chemistry 1981, 256: 6463-6468. PMID: 7240219, DOI: 10.1016/s0021-9258(19)69187-8.
- Functional proteins of the human red blood cell membrane.Marchesi V. Functional proteins of the human red blood cell membrane. Seminars In Hematology 1979, 16: 3-20. PMID: 370984.
- Functional components of surface membranes: potential targets for pharmacological manipulation.Marchesi V. Functional components of surface membranes: potential targets for pharmacological manipulation. Pharmacological Reviews 1978, 30: 371-81. PMID: 392535.
- Recent Membrane Research and its Implications for Clinical MedicineMarchesi V. Recent Membrane Research and its Implications for Clinical Medicine. Annual Review Of Medicine 1978, 29: 593-603. PMID: 348048, DOI: 10.1146/annurev.me.29.020178.003113.
- The anomalous electrophoretic behavior of the major sialoglycoprotein from the human erythrocyte.Silverberg M, Marchesi V. The anomalous electrophoretic behavior of the major sialoglycoprotein from the human erythrocyte. Journal Of Biological Chemistry 1978, 253: 95-98. PMID: 618870, DOI: 10.1016/s0021-9258(17)38274-1.
- Some molecular features of integral membrane proteins.Marchesi V. Some molecular features of integral membrane proteins. Birth Defects 1978, 14: 127-38. PMID: 346076.
- Molecular Features of Glycophorin A: The Major Sialoglycoprotein of the Human Erythrocyte MembraneMARCHESI V. Molecular Features of Glycophorin A: The Major Sialoglycoprotein of the Human Erythrocyte Membrane. Biochemical Society Transactions 1977, 5: 59-59. PMID: 892207, DOI: 10.1042/bst0050059.
- Molecular features of integral membrane proteins of the human red cell membrane.Marchesi V. Molecular features of integral membrane proteins of the human red cell membrane. Advances In Pathobiology 1977, 30-41. PMID: 331915.
- Phosphorylation in membranes of intact human erythrocytes.Shapiro D, Marchesi V. Phosphorylation in membranes of intact human erythrocytes. Journal Of Biological Chemistry 1977, 252: 508-517. PMID: 188816, DOI: 10.1016/s0021-9258(17)32746-1.
- Book ReviewMarchesi V. Book Review. New England Journal Of Medicine 1976, 295: 1486-1486. DOI: 10.1056/nejm197612232952620.
- Book ReviewMarchesi V. Book Review. New England Journal Of Medicine 1976, 294: 1016-1016. DOI: 10.1056/nejm197604292941831.
- Amino-acid sequence and oligosaccharide attachment sites of human erythrocyte glycophorin.Tomita M, Marchesi V. Amino-acid sequence and oligosaccharide attachment sites of human erythrocyte glycophorin. Proceedings Of The National Academy Of Sciences Of The United States Of America 1975, 72: 2964-2968. PMID: 1059087, PMCID: PMC432899, DOI: 10.1073/pnas.72.8.2964.
- Molecular BiologyMarchesi V. Molecular Biology. BioScience 1974, 24: 417-417. DOI: 10.2307/1296914.
- [42] Wheat germ (Triticum vulgaris) agglutininMarchesi V. [42] Wheat germ (Triticum vulgaris) agglutinin. 1972, 28: 354-356. DOI: 10.1016/0076-6879(72)28044-2.
- [22] Isolation of membrane-bound glycoproteins with lithium diiodosalicylateMarchesi V. [22] Isolation of membrane-bound glycoproteins with lithium diiodosalicylate. 1972, 28: 252-254. DOI: 10.1016/0076-6879(72)28024-7.
- Glycoproteins: Isolation from Cell Membranes with Lithium DiiodosalicylateMarchesi V, Andrews E. Glycoproteins: Isolation from Cell Membranes with Lithium Diiodosalicylate. Science 1971, 174: 1247-1248. PMID: 5133448, DOI: 10.1126/science.174.4015.1247.
- Workshop 5 Lymphocyte Recirculation and its Immunological SignificanceFORD W, MARCHESI V. Workshop 5 Lymphocyte Recirculation and its Immunological Significance. 1971, 1159-1164. DOI: 10.1016/b978-0-12-057550-3.50091-0.
- Inactivation of adenosine triphosphatase and disruption of red cell membrances by trypsin: protective effect of adenosine triphosphate.Marchesi V, Palade G. Inactivation of adenosine triphosphatase and disruption of red cell membrances by trypsin: protective effect of adenosine triphosphate. Proceedings Of The National Academy Of Sciences Of The United States Of America 1967, 58: 991-995. PMID: 4228851, PMCID: PMC335737, DOI: 10.1073/pnas.58.3.991.
- ELECTRON MICROSCOPIC STUDIES OF NUCLEOSIDE PHOSPHATASE ACTIVITY IN BLOOD VESSELS AND GLIA OF THE RETINA.MARCHESI V, SEARS M, BARRNETT R. ELECTRON MICROSCOPIC STUDIES OF NUCLEOSIDE PHOSPHATASE ACTIVITY IN BLOOD VESSELS AND GLIA OF THE RETINA. Invest Ophthal 1964, 3: 1-21. PMID: 14121143.
- Morphological changes associated with the extrusion of protein induced in the polymorphonuclear leucocyte by staphylococcal leucocidinWOODIN A, FRENCH J, MARCHESI V. Morphological changes associated with the extrusion of protein induced in the polymorphonuclear leucocyte by staphylococcal leucocidin. Biochemical Journal 1963, 87: 567-571. PMID: 14001784, PMCID: PMC1202001, DOI: 10.1042/bj0870567.
- The possible biochemical lesion in blindness due to methanol poisoningCooper J, Marchesi V. The possible biochemical lesion in blindness due to methanol poisoning. Biochemical Pharmacology 1959, 2: 313-315. PMID: 13811801, DOI: 10.1016/0006-2952(59)90046-2.