A Study of LY3372993 in Participants With Alzheimer's Disease (AD) and Healthy Participants

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3372993 in Participants With Alzheimer's Disease and Healthy Participants

The main purpose of this study is to evaluate the safety and tolerability of LY3372993 in participants with AD, non-Japanese, and Japanese healthy participants who are of first-generation Japanese origin. The study will also investigate how much LY3372993 gets into the bloodstream and will test the effects of LY3372993. The study will be conducted in two parts. The part A includes participants with AD and part B includes healthy participants. Participation could last up to about 61 weeks and may include up to 31 visits to the study center.

Inclusion Criteria:

(Part A)

• Gradual and progressive changes in memory function reported by participants or their partners for greater than or equal to (≥) 6 months at screening, and a clinical diagnosis of mild cognitive impairment due to AD, or AD dementia, as determined by the investigator or based upon medical history
• Mini-Mental State Examination score ≥16
• Have clinical laboratory test results within normal reference range or results with acceptable deviations that are judged to be not clinically significant by the investigator
• Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to study visits or be available through telephone at designated times

(Part B)

• overtly healthy males or females
• have a body mass index of 18.0 to 32.0 kg/m2, inclusive
• To qualify as a participant of the first-generation Japanese origin, the participant, the participant's biological parents, and all of the participant's biological grandparents must be of exclusive Japanese descent and born in Japan.

Exclusion Criteria:

(Part A)

• Have history or presence of uncontrolled asthma, significant autoimmune disease, hereditary angioedema, or known history of common variable immune deficiency
• Contraindication to positron emission tomography (PET)
• Have a history or presence of serious or unstable illnesses including cardiovascular, hepatic, renal, gastrointestinal, respiratory, endocrine, psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study, or increase risk for study intervention administration, or result in a participant's life expectancy of less than (<)24 months
• Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing
• Have had significant medical history of dizziness, syncope, or vasovagal attacks within the past 3 years
• Contraindication to magnetic resonance imaging (MRI), including claustrophobia that cannot be managed with low-dose sedatives or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker

(Part B)

• have a family history of early onset AD (AD diagnosed prior to 65 years of age)
• have used or intend to use over-the-counter or prescription medication including herbal medications within 14 days prior to dosing.
• have a history or presence of significant psychiatric disorders
• have an abnormal blood pressure and/or pulse rate as determined by the investigator, or a pre-existing history of hypertension
• any clinically significant ECG or brain MRI abnormalities