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. Each enrolled participant in Part A will receive a single dose of LY3954068 or placebo (no active drug) given into the spinal fluid. Each participant in Part B will receive 2 doses of either LY3954068 or placebo administered into the spinal fluid. Participants will have the opportunity to join an optional bridging period to a separate potential study where participants would receive LY3954068.

The study will last up to approximately 45 weeks for Part A, and 100 weeks for Part B, including the screening period.

About

Patient Population: Early Alzheimer’s Disease

Study Drug: LY3954068 (Anti-Tau siRNA)

Single intrathecal injections, 5LPs; minimum 2-night stay in DEPRU

Inclusion Criteria

• Have a gradual and progressive change in memory or ability to think and function for more than 6 months prior to screening
• Have a family member or close friend who is with the participant at least 10 hours per week and can participate in study appointments
• Have a mini mental state examination (MMSE) score of 18 to 30 at screening
• Males who agree to follow contraceptive requirements, or women not of childbearing potential

Exclusion Criteria

• Have significant disease affecting the brain other than Alzheimer’s Disease (AD) that could interfere with this study
• Have other serious illnesses that could interfere with this study
• Have certain health conditions that prevent them from getting an MRI or positron emission tomography (PET) scan
• 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