Project Details
Description
Cholinesterases are enzymes involved in the breakdown of acetylcholine, a neurotransmitter, important in brain cell communication, that is reduced in Alzheimer's disease (AD). AD is marked by loss of memory and deposition of abnormal proteins toxic to brain cells that form abnormal structures called amyloid plaques and neurofibrillary tangles. The ability to detect the presence of structures in the living brain could facilitate early diagnosis of the disease. In AD brains, plaques and tangles contain the enzyme butyrylcholinesterase, the presence of which could provide an opportunity for early detection of AD. Therefore, we are developing radiolabelled compounds that bind to butyrylcholinesterase for detection of AD plaques and tangles in the living brain, using PET or SPECT imaging techniques. We have synthesized such compounds with radioactive iodine incorporated into their structures. Our preliminary experiments with these radioactive tracers have shown that they are indeed taken up in abnormally located butyrylcholinesterase "hot spots" in a mouse model of AD. Furthermore, we have been able to visualize abnormal deposits, typical of disease, in donated human AD brain tissue. With this significant advance, we now propose to extend this work, based on these lead imaging compounds, to identify related compounds with even greater ability to detect butyrylcholinesterase associated with plaques and tangles in the AD brain. It is anticipated that butyrylcholinesterase imaging agents will permit early detection of AD signs in the living human brain with non-invasive diagnostic scanning that may lead to development of effective new treatment for AD.
Status | Finished |
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Effective start/end date | 4/1/17 → 3/31/22 |
Funding
- Institute of Aging: US$1,145,813.00
ASJC Scopus Subject Areas
- Clinical Neurology
- Neurology
- Ageing
- Medicine (miscellaneous)