Intervention: Nitric Oxide
Trial phase: Early Phase 1
ATC code: R07AX01
SMILES: [N]=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 18
Group description: The enrolled subjects, both with AD and cognitively normal, will have LPS (0.4 ng/kg) administered intravenously

LPS: LPS (0.4 ng/kg)
Eligibility criteria:
Inclusion Criteria:

Mild AD Subjects:
National Institute on Aging (NIA)-Alzheimer's Association core clinical criteria for probable AD
Age between 55 and 90 (inclusive)
Score on the Montreal Cognitive Assessment (MOCA) greater than or equal to 17
Presence of a responsible caregiver who will accompany AD subjects to all procedures.
Biomarker evidence of Alzheimer's disease via an amyloid PET scan or cerebrospinal fluid (CSF) amyloid Beta measurement.
The patient should have the capacity to consent.
Clinical Dementia Rating (CDR) global score greater than 0.
Cognitively normal elderly Subjects:
Absence of National Institute on Aging-Alzheimer's Association core clinical criteria for probable AD
Objective memory scores within the normal range for age (do not meet MCI Subjects criterion 2)
Age between 55 and 90 (inclusive)
Clinical Dementia Rating (CDR) global score of 0.0

Exclusion Criteria:

Any significant neurologic disease (other than probable AD in the AD Subjects group), such as stroke, Parkinson's disease, brain tumor, seizure disorder, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits.
Any significant systemic disease including hepatic failure, heart failure, renal failure, chronic obstructive pulmonary disease (COPD), active infection and autoimmune disease.
Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded.
Any significant systemic illness or unstable medical condition, including uncontrolled or insulin- dependent diabetes mellitus, uncorrected hypothyroidism or hyperthyroidism, or systemic cancer.
Current or regular use of over-the-counter medication that may affect the immune system (e.g., ibuprofen), including corticosteroids or immunosuppressant drugs; no use in 3 weeks prior to the PET scan
Investigational agents are prohibited 4 weeks prior to entry and for the duration of the study.
Previous treatment with an investigational small molecule with anti-amyloid properties or passive immunization against amyloid within 1 year of study entry.
Previous treatment with an active immunization against amyloid.
History of schizophrenia or other major psychiatric disorder (DSM IV criteria).
History of alcohol or substance abuse or dependence (DSM IV criteria) within the past 2 years.
Clinically significant abnormalities on screening laboratory tests (B12, Thyroid function tests, hematology, chemistry, urinalysis, ECG).
Pregnancy, as determined by screening pregnancy tests for pre-menopausal females
Impairment of visual or auditory acuity sufficient to interfere with study procedures.
Education level < 6 years.
Evidence of current depression as defined by a score of ≥ 5 on the Geriatric Depression Scale.
Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body. The presence of claustrophobia, precluding MRI.
Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the subject in any given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1.
Vaccination in the last month.
Drink more than 5 alcoholic drinks per week or any heavy drinking days in the last 30 days.
BMI > 35 or < 19
Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptive sponge, double barrier [diaphragm or condom plus spermicide], or Intrauterine Device (IUD)
Individuals who are classified as "low binders" for the rs6971 polymorphism (<10% of the population)
Patients on antiplatelet and anticoagulant medications will be excluded.
Any patient without the capacity to consent will be excluded.
Unstable hypertension. If blood pressure is greater than 160/100, the investigators will contact the subject's primary care physician to manage their blood pressure. If their blood pressure is not reduced to be consistently below 160/100 by the scanning day the subject will be excluded from the protocol.
Patients with contraindications for lumbar puncture procedure can be still involved and will be excluded from the optional portion of the study with the lumbar puncture. These include existing intracranial space-occupying lesion with mass effect, posterior fossa mass, risk of cerebral herniation by increased CSF pressure or Arnold chiari malformation, as well as anticoagulant medication, coagulopathies and uncorrected bleeding diathesis, congenital spine abnormalities, and local skin infection at the puncture site.