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2007 Grant - Ghiso
Signature Markers of Beta-Amyloid Degradation
Jorge A. Ghiso, Ph.D.
New York University School of Medicine
New York, New York
2007 Investigator-Initiated Research Grant
Researchers have long been interested in identifying biological markers of Alzheimer's disease, molecules in the blood or cerebrospinal fluid (CSF)
that would indicate the presence and progression of Alzheimer's disease pathology. Such markers would be valuable for diagnostic and treatment-monitoring tools.
Beta-amyloid, a key suspect in Alzheimer's disease pathology, is produced when it is clipped from a parent protein. A single beta-amyloid molecule is soluble, and normal processes clear it from the brain.
In the Alzheimer's disease, the production of beta-amyloid molecules and the clearance mechanisms are somehow out of balance. Beta-amyloid molecules accumulate and assemble themselves into toxic structures.
In previous studies of tissues from autopsied Alzheimer brains, Jorge A. Ghiso, Ph.D., and colleagues found small pieces of beta-amyloid — the apparent remnants of molecular activities trying to break down beta-amyloid structures. These remnants were also found in the CSF of people with Alzheimer's disease.
In this current project, the investigators will expand this work. Using a larger sample of brain tissue, they will identify and correlate the presence of beta-amyloid remnants with the presence of beta-amyloid aggregates. They will also determine whether these remnants are present in the CSF of Alzheimer-like mice and whether the level of remnants in CSF is a useful measure of the progression of brain pathology. This work may lay the foundation for devel-oping tools to assess disease progression in people living with Alzheimer's.