A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of DNL921 in Healthy Participants and Participants With Alzheimer's Disease

Key Inclusion Criteria (Healthy Participants):

• Are male or female of non-childbearing potential and are aged 18 through 60 years at the time of screening
• Have a BMI of 18 through 32 kg/m2 and a body weight of at least 50 kg
• For female participants: Are of non-childbearing potential
• For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception

Key Exclusion Criteria (Healthy Participants):

• Have any history of clinically significant neurological, psychiatric, endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, immunological, or allergic disease, or other major disorders
• Have a positive serum pregnancy test or are currently lactating or breastfeeding
• Have been hospitalized during the 4 weeks prior to screening

Key Inclusion Criteria (Participants with AD):

• Are male or female of non-childbearing potential and aged 50 to 75 years at the time of screening
• Have a BMI between 18 and 32 kg/m2 and a body weight of at least 45 kg
• Have a diagnosis of probable mild to moderate AD dementia based on NIA AA 2011 criteria, including amnestic or nonamnestic presentation at screening or prodromal AD (consistent with the NIA-AA diagnostic criteria and guidelines for mild cognitive impairment due to AD)
• Have supportive evidence of AD pathology by the following:

• Plasma ptau217/Abeta42 positive
• Positive amyloid PET scan
• For female participants: Are of non-childbearing potential
• For male participants: Are surgically sterile by bilateral orchidectomy, or are abstinent, or agree to use two acceptable forms of contraception

Key Exclusion Criteria (Participants with AD):

• Have other clinically significant neurological or cognitive disorders affecting the CNS, as determined by the investigator, other than AD
• Have specific psychiatric conditions
• Have any history of unstable or poorly controlled endocrine, pulmonary, cardiovascular, gastrointestinal, hepatic, hematological, or other significant medical condition that, in the opinion of the investigator, may interfere with the completion or interpretation of study assessment
• Have had a malignancy within 5 years before screening, except fully resected basal cell carcinoma or other malignancies treated with curative intent (such as prostate cancer) at low risk of recurrence
• Have a positive serum pregnancy test or are currently lactating or breastfeeding
• Have been hospitalized during the 4 weeks prior to screening
• Have had previous anti-amyloid or anti-tau immunotherapy (including active immunization) or have participated in experimental gene therapy or cell therapy at any time