This study evaluates the use of [18F]F-AraG PET/CT imaging to quantify activated T cell involvement in patients with Alzheimer's disease (AD). Participants will undergo total-body dynamic PET imaging to assess tracer uptake in the brain and peripheral organs. Results will be compared between participants with AD and healthy controls to characterize both central nervous system and systemic immune alterations in AD

Alzheimer's disease (AD) is known to involve neuroinflammation, but the role of T cell-mediated adaptive immunity remains poorly understood. This study uses [18F]F-AraG, a PET tracer that preferentially accumulates in activated T cells, to noninvasively assess immune-metabolic activity in the brain and peripheral organs in patients with AD.

Participants will undergo high-sensitivity total-body dynamic PET imaging using the uEXPLORER system. Intracerebral and systemic immune-metabolic activity will be assessed by analyzing total body [18F]F-AraG biodistribution and kinetics. .

The study will compare imaging metrics between AD participants and healthy controls.

Inclusion Criteria:

1. Age ≥ 55 years
2. Prior volumetric brain MRI available. If the prior MRI scan is not acquired within 6 months of [18F]F-AraG imaging or if the investigator determines that prior MRI scan cannot be used, a new MRI scan will be acquired.
3. Able to tolerate a PET scan, and willingness and ability to comply with all protocol required procedures.
4. For participants of reproductive potential - defined as individuals who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months), or who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy or bilateral salpingectomy - willingness to use effective double barrier contraceptive methods (excluding withdrawal or timing methods) up to 1 day after the administration of [18F]F-AraG
5. Subjects with possible or probable AD based on the NIA-Alzheimer's Association working group's diagnostic guidelines for AD.
6. Have a study partner who has significant interaction with the subject and can report on the subject's activities of daily living.

Exclusion Criteria:

1. Clinically significant psychiatric disease other than depression.
2. Structural brain abnormalities on MRI (e.g. large infarct or mass) likely to interfere with interpretation of a PET scan.
3. History of significant alcohol or substance abuse/dependence within the past 5 years.
4. Non-study related radiopharmaceutical imaging or treatment procedure within 7 days prior to the PET imaging session.
5. Current or recent investigational drug use, defined as receiving any investigational medications or participation in another investigational drug trial within the last 30 days.
6. Serious comorbidities (malignant and nonmalignant disease or other conditions) that in the opinion of the investigator could compromise study objectives.
7. Conditions affecting immune function or conditions caused by immune system malfunction that could interfere with imaging, including known inflammatory or immune disorders, systemic malignancy, or chronic viral infections.
8. Pregnant or nursing individuals. All participants of reproductive potential will undergo a urine or HCG serum pregnancy test with a sensitivity of at least 25 mIU/mL at screening and on the day of PET/CT imaging.
9. Prior allogeneic stem cell or solid organ transplant.
10. Previously diagnosed myelodysplasia syndrome or history of lymphoproliferative disease prior to study entry.
11. Active systemic autoimmune diseases.
12. Self-reported history of dysphoria or anxiety in closed spaces (i.e., uncontrolled claustrophobia).
13. Concurrent or prior enrollment in a separate research study involving a PET scan performed within the last 12 months for research purposes only.
14. Body weight is more than 240 kg (529 pounds)
15. Recent use of medications containing guanosine or cysteine analogs.
16. Any other criteria which would make the participant unsuitable for study participation, as determined by the Principal Investigator.