Overview

This research study is being done to learn more about inflammation in the brain using Positron Emission Tomography/Computed Tomography (PET/CT) imaging in people with Alzheimer's Disease/Mild Cognitive Impairment or healthy controls.

If the subject agrees to be in this study, she/ he will have a PET/CT scan using the investigational radiotracer [18F]NOS. A subject with a specific genetic polymorphism may also agree to be in the sub-study in which she/he will have another PET/CT scan using the investigational tracer [11C]PBR28 for comparison with the FNOS [18F]NOS scan. For subjects who agree to this sub-study they may undergo the brain PET/CT scan with [11C]PBR28 either on the same day as the [18F]NOS PET/CT or on another day. The subject may have a screening visit before the PET/CT scan visit if the investigator needs to confirm the subject is able to be in the study.

A blood sample will be taken before the scans. Additional blood samples will be taken during the PET scans. Subjects must also agree to have an MRI scan for this research study if she/he has not had a recent scan that the study doctor decides can be used for this study.

Eligibility

Inclusion Criteria (HC cohort only):

1. - Males and females ≥ 55 years of age
2. Part of the UPenn ADC research cohort with designation of cognitively normal per ADC database.
3. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be negative by the study PI.
4. Mini-mental status exam (MMSE) score of 28 or higher per ADC database.
5. Participants must be informed of the investigational nature of this study and be willing to provide written informed consent and participate in this study in accordance with institutional and federal guidelines prior to study-specific procedures.

Inclusion Criteria (AD/MCI cohort only)

1. Males and females ≥ 55 years of age
2. Part of the Upenn ADC research cohort with designation that the presence of Alzheimer's pathology is likely per ADC database.
3. A brain amyloid PET scan ≤ 1 year prior to enrollment in this study that is determined to be positive by the study PI.
4. Mini-mental status exam (MMSE) score of 14-27 per ADC database.
5. Subjects must have a designated study partner to accompany them to study visits

Inclusion Criteria 11C-PBR28 sub-study (both HC and AD/MCI cohorts)

1. High affinity carrier of the rs6971 TSPO polymorphism (whole genome sequencing is available from the UPenn ADC research cohort and will be interrogated for this polymorphism)

Exclusion Criteria (HC and PD cohorts):

1. Females of child-bearing potential will not be included, female subjects must be post-menopausal or surgically sterile
2. History of epilepsy or seizure disorder as assessed by medical record review and/or self-report
3. History of head trauma or evidence of structural abnormalities such as a major stroke or mass on MRI that in the opinion of an investigator may interfere with the uptake of applicable radiotracer as assessed by medical record review and/or self-report
4. Current tobacco or nicotine dependence. History of greater than 5 pack years of smoking and less than 2 years since smoking cessation.
5. Have a history of significant or ongoing alcohol abuse or substance abuse or dependence based on medical record review or self-reported
6. Inability to tolerate imaging procedures in the opinion of an investigator or treating physician
7. Any current medical condition, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician or investigator to be a condition that could compromise participant safety or successful participation in the study