Overview

The main purpose of this study is to evaluate the safety of LY3954068 in participants with early symptomatic Alzheimer's Disease (AD). The study will also investigate how much LY3954068 gets into the bloodstream and will test the effects of LY3954068 on markers of AD.

The study will be comprised of two parts, A and B. Part B is optional, and participants from Part A may also have the opportunity to join an optional bridging period to a separate potential study where participants would receive LY3954068. Each enrolled participant in Part A will receive a single dose of LY3954068 or placebo (no active drug) given into the spinal fluid. If conducted, each participant in Part B would receive 2 doses of either LY3954068 or placebo administered into the spinal fluid.

The study will last up to approximately 45 weeks for Part A, and, if conducted, 73 weeks for Part B, including the screening period.

If the optional bridging period is conducted, participants in Part A could be enrolled in the separate potential study for up to approximately 96 weeks, including the screening period.

Eligibility

Inclusion Criteria:

• Have a body mass index (BMI) within the range 18 (17 for Japan participants) to 40 kilograms per square meter (kg/m²), inclusive, at screening.
• Have gradual and progressive change in memory function for greater than or equal to (≥) 6 months as reported by the participant or informant.
• Have a mini mental state examination (MMSE) score of 18 to 30 at screening.
• Have a clinical dementia rating (CDR) global score of 0.5 to 1.0, with a memory box score ≥ 0.5 at screening.
• Meet flortaucipir F18 positron emission tomography (PET) criteria, as defined in the TAUVID™ FDA label (TAUVID™ prescribing information, 2024), demonstrating evidence of tau pathology.
• Males who agree to follow contraceptive requirements, or women not of childbearing potential (WNOCBP).
• Participants must have up to 2 study partners who are with contact with the participant at least 10 hours per week and one of whom can attend study appointments.

Exclusion Criteria:

• Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (other than Alzheimer's Disease), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of less than (<)24 months.
• Have a sensitivity to flortaucipir F18.
• Have contraindication to magnetic resonance imaging (MRI), including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
• Have a current exposure to an amyloid targeted therapy (ATT). Prior exposure to ATTs greater than 1 year from the last dose may be permitted at the discretion of the investigator and in consultation with the sponsor.
• Have previous exposure to any Investigational Medicinal Product administered intrathecal (IT) or previous exposure to any anti-tau therapy.
• Have a history of clinically significant back pain, back pathology and/or back injury (for example, degenerative disease, spinal deformity or spinal surgery) that may predispose to complications or technical difficulty with lumbar puncture.