A Study to Learn About the Safety of BIIB080 and Whether it Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age

Open to people ages 50-80

for Placebo-controlled Period:

- Must meet all the clinical staging criteria for MCI due to AD (Stage 3) or mild AD dementia (Stage 4) according to the National Institute on Aging at National Institutes of Health and the Alzheimer's Association (NIA-AA) and must have the following at Screening Visit 1: 1. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Delayed Memory Index score of ≤85, indicative of objective evidence of memory impairment. 2. CDR global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD dementia 3. MMSE score of 21 to 30 (inclusive). 4. CDR Memory Box score of ≥0.5. - Evidence of amyloid pathology as measured by positive emission tomography (PET) or cerebrospinal fluid (CSF) sampling. - Must have 1 care partner who, in the Investigator's judgment, has frequent and sufficient contact with the participant (at least 10 hours/week) to be able to provide accurate information about the participant's cognitive and functional abilities. Key Inclusion Criteria for LTE Period - Participants must have completed the placebo-controlled period of the study, including the Week 76 visit. - Participants must have taken at least 5 doses of BIIB080 or placebo during the placebo-controlled period. - MMSE score >10 at the Week 76 visit. - Must have 1 care partner who, in the Investigator's judgment, has frequent and sufficient contact with the participant (at least 10 hours/week) to be able to provide accurate information about the participant's cognitive and functional abilities.

for Placebo-controlled Period:

- Known allergy to BIIB080 or a history of hypersensitivity to any of the inactive ingredients in the drug product. - Previous participation in this study or previous studies with BIIB080. - Use of non-disease-modifying AD medications (including but not limited to donepezil, rivastigmine, galantamine, tacrine, and memantine) at doses that have not been stable for at least 8 weeks prior to Screening Visit 1 and during the screening period up to Day 1. - Use of any commercially available disease-modifying AD medications such as anti-amyloid monoclonal antibodies. - Prior participation in any active or passive immunotherapy study targeting Aβ, unless documentation of receipt of placebo is available. - Prior participation in any passive immunotherapy study targeting tau, unless the last administration occurred 6 months or 5 half-lives, whichever is sooner, prior to Screening or documentation of receipt of placebo is available. - Prior participation in any study involving an investigational treatment targeting tau that is not a passive immunotherapy, unless documentation of receipt of placebo is available. - Prior participation in a study of any other agent(s) not included in exclusion criteria 5, 6, and 7 with a purported disease-modifying effect in AD within 12 months, unless documentation of receipt of placebo is available. - Prior participation in a study of any gene therapy with a purported disease-modifying effect in AD, unless documentation of receipt of placebo is available. - Current use or previous use of medications with a purported disease-modifying effect in AD, outside of investigational studies. - Any vaccination given within 10 days prior to Day -1. Coronavirus disease 2019 (COVID-19) vaccinations using RNA or deoxyribonucleic acid (DNA) technology are allowed during the study, as well as other types of immunization/vaccination/booster, except during the 10 days before and after clinic visits. - Contraindications to having a brain magnetic resonance imaging (MRI) [e.g., MRI-incompatible pacemaker; MRI-incompatible aneurysm clips, artificial heart valves, or other metal foreign body; claustrophobia that cannot be medically managed]. If the MRI compatibility of implanted devices is unknown, the participant must be excluded from the study. - Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 52 weeks prior to the Baseline Visit. Key Exclusion Criteria for LTE Period - Any medical or psychiatric contraindication or clinically significant abnormality that, in the opinion of the Investigator, will substantially increase the risk associated with the participant's enrollment in and completion of the study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.