Biomarkers of Alzheimer's disease (AD) have recently become extremely important for a number of reasons: to improve diagnosis, to measure severity of disease, to measure progression of disease, to measure effects of novel disease-modifying drugs and to speed development of these novel experimental drugs by reducing time needed to follow patients, number of patients to be followed per study, and cost of research. (Thal, 2006, Nichols, 2006)~The neuropathology of AD is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss (Braak and Braak, 1997). Amyloid plaques are believed to play an integral role in AD (Selkoe, 1993). Plaques are neurotoxic (Yankner, 1989). Elevated levels of Aβ in the brain are correlated with cognitive decline (Naslund, 2000). Removal of plaques in animal models of AD results in behavioral improvements (Arendash, 2001).~There are no approved in vivo markers of amyloid load in humans. Several compounds with affinity for binding amyloid in vivo are under investigation. All of these compounds use radioactive chemical tags for positron emission tomography (PET) imaging. Attempts at finding non-radioactive amyloid tracers are underway, but still poorly developed. The most promising compound is 11C-PIB. Pittsburgh Compound-B has statistically significant increased retention in AD cortical areas, relative to controls (P<0.05). (Price, 2005) To our knowledge, 11C-PIB imaging has not been compared against frontotemporal dementia (FTD) controls.~We will recruit (from our clinic population), a total of 30 subjects, 10 from each of the following 3 diagnostic categories: frontotemporal dementia, Alzheimer's disease, and normal volunteers. All subjects will be given an FDG-PET scan (if they haven't had one in the past) and a PIB-PET scan.~Objective and Hypothesis:~The overall objective of this project is to study the biodistribution of 11C-PIB using PET imaging in normal elderly volunteers and relevant patient groups. Comparison with FDG-PET is essential to confirm group membership and for anatomic co-registration of 11C-PIB images.~Specific Aim 1: Determine the biodistribution of 11C-PIB in AD, FTD, and cognitively normal elderly individuals and determine whether it reflects the distribution of amyloid plaques in the brain expected from postmortem studies.~Hypothesis 1: The agent 11C-PIB has similar biodistribution outside the brain in AD, FTD, and cognitively normal elderly individuals.~Hypothesis 2: Patients with AD scanned with 11C-PIB will have higher standardized uptake values (SUVs) than cognitively normal elderly in brain regions where beta amyloid are expected to be over-expressed.~Hypothesis 3: Patients with FTD scanned with 11C-PIB will have similar standardized uptake values (SUVs) as cognitively normal elderly subjects and lower values than in AD subjects in brain regions where beta amyloid are expected in AD to be overexpressed.~Specific Aim 2: Correlate glucose metabolism with 11C-PIB PET results.~Hypothesis 4: Patients with a pattern of glucose hypometabolism suggestive of FTD with FDG-PET have 11C-PIB uptake and brain biodistribution similar to cognitively normal elderly, while those with a pattern of glucose hypometabolism suggestive of AD have abnormal PIB uptake and brain biodistribution of 11C-PIB
Alzheimer's disease (AD) is characterized by neuritic plaques, neurofibrillary tangles, and neuronal cell loss. Amyloid plaques are believed to play an integral role in AD. Elevated levels of Aβ in the brain are correlated with cognitive decline.~There are no approved ways to measure amyloid load in humans. Several compounds are under investigation. All of these compounds use radioactive chemical tags for positron emission tomography (PET) imaging. The most promising compound is 11C-PIB, or Pittsburgh Compound-B. This compound can be injected and a PET scan performed. This allows doctors to see the amyloid plaques in the brain, and to use this information to look at other types of dementia to see if there are differences and/or similarities in the plaques.~We will recruit a total of 30 subjects, 10 from each of the following three diagnostic categories: frontotemporal dementia (FTD), Alzheimer's disease, and normal volunteers. All subjects will be given an [18F]fluorodeoxyglucose or FDG-PET scan (if they haven't had one in the past) and a PIB-PET scan.~The overall objective of this project is to study the biodistribution of 11C-PIB using PET imaging in normal elderly volunteers and relevant patient groups.