Single-Ascending-Dose Study of BIIB076 in Healthy Volunteers and Participants With Alzheimer's Disease

Key Inclusion Criteria - Healthy Participants

- Must be in good health as determined by the Investigator, based on medical history and
Screening evaluations.

Key Inclusion Criteria - Participants with Alzheimer's Disease (AD)

- Must have a clinical diagnosis of mild AD consistent with the following:

- Probable AD, according to the National Institute on Aging - Alzheimer's Association
workgroups on diagnostic guidelines for AD criteria [McKhann 2011].

- CSF concentrations of Aβ42, t-tau, and p-tau consistent with diagnosis of AD.

- Must have a Mini-Mental State Examination score between 20 and 26 (inclusive) at
Screening.

Key Exclusion Criteria - Healthy Participants

- Brain MRI findings that might pose a risk to the participant, or might prevent a
satisfactory MRI assessment for safety monitoring.

- History of any clinically significant cardiac, endocrine, gastrointestinal,
hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic,
dermatologic, psychiatric, or renal disease, or other major disease, as determined by
the Investigator.

- Current enrollment in any other drug, biologic, device, or clinical study or treatment
with an investigational drug or approved therapy for investigational use within 30
days (6 months for biologics) or 5 half-lives, whichever is longer, prior to Day-1.

- Contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible aneurysm
clips, artificial heart valves, or other metal foreign body; claustrophobia that
cannot be medically managed).

- Contraindications to having an Lumbar Puncture (LP).

Key Exclusion Criteria - Participants with Alzheimer's Disease (AD)

- Any medical or neurologic/neurodegenerative condition (other than AD) that, in the
opinion of the Investigator, might be a contributing cause to the participant's
cognitive impairment (e.g.,current history of substance abuse, uncontrolled vitamin
B12 deficiency or uncontrolled thyroid disease, stroke or other cerebrovascular
condition, Parkinson's disease, Lewy body dementia, or frontotemporal dementia or head
trauma), or could lead to discontinuation, noncompliance with study assessments, or
safety concerns.

- Diagnosis within 1 year prior to Screening and/or evidence of clinically significant
(in the opinion of the Investigator) psychiatric illness including uncontrolled major
depression, bipolar affective disorder, other psychiatric illness, and suicidal
ideation.

- Any documented prior history of chronic schizophrenia.

- History of any clinically significant cardiac, endocrine, gastrointestinal,
hematologic, hepatic, immunologic, metabolic, urologic, pulmonary (including chronic
obstructive pulmonary disease), neurologic, dermatologic, or renal disease, or other
major disease, as determined by the Investigator.

- Use of any medications for the treatment of comorbid conditions that have not been
stable for at least 3 months prior to Day -1 and/or that are not expected to remain
stable for the duration of the study.

- Current enrollment or plan to enroll in any other drug, biologic, device, or clinical
study or treatment with an investigational drug or approved therapy for
investigational use within 30 days (6 months for biologics) or 5 half-lives, whichever
is longer, prior to Day-1.

- Contraindications to having a brain MRI (e.g., pacemaker; MRI-incompatible aneurysm
clips, artificial heart valves, or other metal foreign body; claustrophobia that
cannot be medically managed).

- Brain MRI findings that might be a contributing cause of the participant's dementia,
might pose a risk to the participant, or might prevent a satisfactory MRI assessment
for safety monitoring.

- Contraindications to having an LP.

- History of, or ongoing chronic uncontrolled hypertension

- History of unstable angina, myocardial infarction, chronic heart failure (New York
Heart Association Class 3 or 4), or clinically significant conduction abnormalities
(e.g., unstable atrial fibrillation) within 1 year prior to Day -1.

- Medications with platelet anti-aggregant or anticoagulant properties, except the use
of aspirin at a dose ≤325 mg per day.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.