Intervention: N88C2T6Ybp
Trial phase: Phase 1
SMILES: CN1Cc2ccc(-c3nc(C#N)ccc3-c3cnn(CC4(C)CCCC4)c3)cc2C1=O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 10
Group description: Participants with AD receive a single IV dose of ~370 MBq [11C]MK-6884 in Part 3 of the study.
Eligibility criteria:
Inclusion Criteria:

Part 1, 2 and 3:

Male, or non-pregnant and non-breast feeding female of 18 to 55 years of age (Part 1) or 55 to 85 years of age (Parts 2 and 3); in addition:

Male participant who is sexually active with females of childbearing potential must be willing to use a condom from the first dose of study drug until 3 months post the last dose of study drug
Female participant with reproductive potential must have serum β-human chorionic gonadotropin (β-hCG) test result consistent with non-pregnant state at screening and agree to use two acceptable methods of birth control beginning at screening visit, during study and until 2 weeks after the last dose of study drug
Female participant of non-childbearing potential must be post-menopausal female (participant has been without menses for at least 1 year and has a follicle stimulating hormone [FSH] level in the postmenopausal range at screening), or surgically sterile female (status post hysterectomy, oophorectomy, or tubal ligation)
Body Mass Index (BMI) ≤35 kg/m^2, with height ≤195 cm and weight ≤136 kg
In good health (Part 1) or generally healthy (Parts 2 and 3) based on medical history, physical examination, vital sign measurements and electrocardiogram (ECG)
Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 3 months

Part 2 Only:

Willing to allow placement of an arterial catheter in the radial artery
Mini Mental Status Examination (MMSE) score ≥27
No history of subjective memory or other cognitive complaints
No objective evidence of memory or cognitive impairment

Part 3 Only:

Moderate to severe AD as defined by:

MMSE score ≤20
Meets National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD
Meets Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria for AD
Rosen-Modified Hachinski score ≤4
Screening magnetic resonance imaging (MRI) scan consistent with a diagnosis of AD
Clear history of cognitive and functional decline over ≥1 year
On a stable dose of one of protocol-defined acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil and rivastigmine) for symptomatic treatment of AD. Dose must be stable for at least the last 4 weeks before screening
Has a reliable trial partner/caregiver who is able to accompany the participant to all clinic visits, if needed, and able to provide information to study investigator/staff via telephone contact

Exclusion Criteria:

Part 1, 2, and 3:

Mentally or legally incapacitated, has significant emotional problems at the time of screening visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years, except (for Part 3 only) for psychiatric disorders associated with AD
History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases, unless (for Part 2 and 3 only) adequately controlled through a stable medication regimen
History of cancer
History of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. For Part 2, this includes any known allergy to lidocaine which may be used as an anesthetic for the placement of the arterial catheter
Has positive test result for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
Has had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to screening
Has participated in another investigational trial within 4 weeks of screening
Corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females)
Is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies, beginning approximately 2 weeks prior to administration of the initial dose of study drug and throughout the study.
Consumes >3 servings of alcohol a day
Consumes >6 caffeine servings a day
Is currently a regular or recreational user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months
Has participated in a PET research study or other study involving administration of a radioactive substance or ionizing radiation within 12 months prior to screening or has undergone an extensive radiological examination within this period
Suffers from claustrophobia or an inability to tolerate confinement in small places and would be unable to undergo MRI or PET scanning

Part 2 Only:

- Has been administered an AChEI within the prior 3 months or will require administration of an AChEI during study

Part 3 Only:

Has been administered galantamine within the prior 7 days or will require administration of galantamine during study
History within 2 years prior to screening, or current evidence of any neurological or neurodegenerative disorder other than AD that is associated with transient or sustained alterations in cognition
History within 2 years prior to screening, or current evidence of a psychotic disorder or a major depressive disorder

Part 2 and 3 Only:

- Has or is suspected to have implanted or embedded metal objects, or fragments in the head or body that would present a risk during the MRI scanning procedure