Selective PET Imaging of Astrocytes and Microglia in Alzheimer's Disease
The Methodist Hospital Research Institute
Summary
Inflammation occurs in many brain diseases including Alzheimer's disease. In Alzheimer's disease, an abnormal protein called amyloid starts accumulating decades before the start of forgetfulness. However, scientists have reported that inflammation but not amyloid is linked to forgetfulness and the topography of brain inflammation and tau buildup are closely correlated in patients with mild cognitive impairment due to Alzheimer's disease. New medications are under development to help healing and prevent permanent damage in the brain. To see if inflammation is improving or getting worse with these medications, investigators can watch inside of the brain using a special camera called positron emission tomography (PET). It is currently possible to watch inflammation in the brain by taking pictures of a molecule called translocator protein (TSPO). But the problem is that by imaging TSPO, investigators can catch changes in more than one kind of cells. The information is not specific to each cell type. Such vague information is not completely useful to monitor the effect of new medications for inflammation. This proposal attempts to develop a novel method to capture changes in each of two major players in inflammation, microglia and astrocytes. To do so, investigators will take selective pictures of one cell type by using a novel imaging agent for PET. Investigators will also take PET pictures of TSPO. Investigators will process these two kinds of PET pictures using advanced mathematical methods and extract specific information on microglia and astrocytes. Our novel method will be useful to monitor new therapies to treat inflammation in the brain.
Description
Inflammation in brain plays critical roles in disease progress and symptom development in a number of brain disorders such as Alzheimer's disease (AD), traumatic brain injury, major depressive disorder, epilepsy, and schizophrenia. Neuroinflammation has been imaged using positron emission tomography (PET) by using translocator protein (TSPO) as the marker. Although TSPO PET studies have provided insight to understand the pathology, some results are difficult to interpret. TSPO imaging has a major limitation of not being selective to one type of glia; it is expressed by both microglia and astro…
Eligibility
- Age range
- 18–90 years
- Sex
- All
- Healthy volunteers
- Yes
Patients with Alzheimer's disease Inclusion criteria: * Individuals of either sex, 50-90 years of age. * Meeting research criteria for AD (McKhann, Knopman et al. 2011). * With a CDR (Morris 1993) score of 1-3. * Fluent in English or Spanish. * Have sufficient communication and comprehension ability to consent to the performance of the study or have a legally authorized representative. Exclusion criteria: * Inability to undergo MRI or PET for any reason, including severe claustrophobia. * History of large stroke or brain trauma, multiple sclerosis or other brain disorder that, in the judgm…
Interventions
- DrugPositron Emission Tomography (PET) using 11C-ER176 for TSPO and 18F-SMBT1 for MAO-B
Participants will receive PET with 11C-ER176 to measure microglia AND astrocytes and PET with 18F-SMBT1 to measure astrocytes.
Location
- Houston Methodist Research InstituteHouston, Texas