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2006 Grant - Iqbal
Biomarkers of Neurofibrillary Pathology
Khalid Iqbal, Ph.D.
Research Foundation for Mental Hygiene
New York State Institute for Basic Research
New York, New York
2006 Investigator-Initiated Research Grant
Two characteristic features of Alzheimer pathology are amyloid plaques and neurofibrillary tangles. Amyloid plaques, primarily consisting of deposits of beta-amyloid protein fragments, exist in the spaces outside of nerve cells in the brain. Neurofibrillary tangles, made of abnormal aggregates of the protein tau, are inside nerve cells.
In Alzheimer's disease, normal chemical modifications of tau go unchecked. These overly modified proteins then form tangles. Studies have shown that people with Alzheimer's disease may have high levels of abnormal tau in the cerebrospinal fluid (CSF), which surrounds the brain and the spinal cord. Levels of beta-amyloid, on the other hand, seem to be low in CSF, possibly because it is deposited into amyloid plaques during the disease process.
Khalid Iqbal, Ph.D., and colleagues are developing methods to measure tau and beta-amyloid in CSF. These tests may be useful for diagnosing Alzheimer's disease and monitoring disease progression. Their strategy is to create antibody-based tests that can detect these proteins, as well as another protein called ubiquitin, which attaches itself to abnormal tau, neurofibrillary tangles and amyloid plaques.
The investigators will evaluate the usefulness of their tests for diagnosing Alzheimer's. In addition, these diagnostic tools may be able to distinguish among different types of abnormal tau, which may be a first step toward identifying different forms of the disease.