Brain Imaging in Elderly People and Individuals With Alzheimer's Disease
Summary
The purpose of this study is to use brain imaging technology to study the effects of aging and Alzheimer's Disease (AD) on a specific type of brain receptor.
The brain is made up of cells called neurons. The neurons communicate with one another and secrete chemicals called neurotransmitters. The neurotransmitters bind to specific sites on other neurons called receptors. Acetylcholine (ACh) is a neurotransmitter that binds to ACh receptors. In both aging and AD, the number of neurons that secrete ACh decreases and the function of some ACh receptors changes. This study will use positron emission tomography (PET) scans of the brain to study the effects of age and AD on muscarinic type 2 [M2], a type of ACh receptor.
Participants in this study will be injected with a radioactive tracer (ligand [F-18] FP-TZTP) which binds to [M2] receptors. Participants will then undergo a PET scan in order for the density and function of [M2] receptors to be studied.
Description
The Geriatric Psychiatry Branch (GPB) of the National Institute of Mental Health (NIMH) proposes to study the effect of aging and Alzheimer's Disease (AD) on muscarinic type 2 (M2) receptor density and function using the ligand [F-18] FP-TZTP. M2 receptors are primarily autoreceptors found on acetylcholine (ACh) neurons, and are lost along with ACh neurons in aging and AD, particularly in the cerebral cortex. As we near completion of the study of the young versus the old, we would like to add a few more healthy subjects to achieve better gender balance, continue the accrual of Alzheimer's patients and expand the Protocol to include its natural scientific progression. Quantification of M2 receptors with a single FP-TZTP scan as we are currently performing with 99-M-0073 provides a measure of the number of cholinergic receptors in the brain, but not their capacity to release acetylcholine into the synapse. To test this capacity requires a second TZTP scan and the use of an agent that alters acetylcholine concentrations in the synapse. Non-human primate studies performed here (1) have found PET scans with FP-TZTP to be sensitive to changes in acetylcholine synapse concentrations, as a result of competition, in response to the adminstration of the acetylinesterase inhibitor physostigmine. We would like to use physostigmine in all groups; young, older normal, and Alzheimer's patients to infer differences in capacity to release acetylcholine.
Study Design
N/A
Conditions
Alzheimer's Disease
Intervention
O15, [F-18] FP-TZTP
Location
National Institute of Mental Health (NIMH)
Bethesda
Maryland
United States
20892
Status
Completed
Source
National Institutes of Health Clinical Center (CC)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00001917
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Neuropil Threads
Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.
Alzheimer Vaccines
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
Aphasia, Primary Progressive
A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)
Amyloid Beta-protein Precursor
A precursor to the AMYLOID BETA-PROTEIN (beta/A4). Alterations in the expression of the amyloid beta-protein precursor (ABPP) gene, located on chromosome 21, plays a role in the development of the neuropathology common to both ALZHEIMER DISEASE and DOWN SYNDROME. ABPP is associated with the extensive extracellular matrix secreted by neuronal cells. Upon cleavage, this precursor produces three proteins of varying amino acid lengths: 695, 751, and 770. The beta/A4 (695 amino acids) or beta-amyloid protein is the principal component of the extracellular amyloid in senile plaques found in ALZHEIMER DISEASE; DOWN SYNDROME and, to a limited extent, in normal aging.
Down Syndrome
A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe MENTAL RETARDATION. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)
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PubMed Articles
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Clinical and biomarker changes in Alzheimer's disease.
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Clinical and biomarker changes in Alzheimer's disease.
To the Editor: In reporting the results of the Dominantly Inherited Alzheimer Network (DIAN) study, Bateman and colleagues (Aug. 30 issue)(1) describe clinical and biomarker changes in dominantly inhe...
Dementia: a global health priority - highlights from an ADI and World Health Organization report.
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