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.