A Phase 3b/4 Randomized, Double-Blind, Placebo-Controlled, Parallel- Group Study to Verify the Clinical Benefit of Aducanumab (BIIB037) in Participants with Alzheimer’s Disease

1. The participant and/or his/her legally authorized representative (e.g., parent, spouse, or legal guardian, where local regulations and institutional practices permit) must be able, as appropriate and applicable, to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local privacy and ethics regulations. 2. The participant must be 60 to 85 years old, inclusive, at the time of informed consent. 3. All women of childbearing potential must practice effective contraception during the study and for 5 times the half-life or 24 weeks (whichever is longer) after their last dose of study treatment. For further details of contraceptive requirements for this study, refer to Section 11.5. 4. The participant must have a minimum of 9 years of education or vocational training or the equivalent education/vocational training until the age of 15 or, per Investigator judgment, work experience that indicates a lack of mental deficits other than early-stage dementia. 5. The participant must have confirmed amyloid beta pathology by CSF (historical CSF test results not allowed) or amyloid PET. If providing only a screening amyloid PET scan for amyloid positivity, a historical, amyloid PET scan obtained within 18 months of Screening Visit 2 is permissible. Sponsor-approved tracers must be used and scans must be submitted to the central imaging vendor to confirm that study inclusion criteria are met. In the case of discordant results between CSF and PET, PET results will be used to assess eligibility. 6. The participant must have a history of subjective memory decline with gradual onset and slow progression over the last 6 months before Screening, confirmed by study partner. 7. The participant must meet all of the following clinical criteria for MCI due to Alzheimer’s disease or mild Alzheimer’s disease according to NIA-AA criteria: • Have an MMSE score between 22 and 30 inclusive • Have a CDR memory score ≥ 0.5 • Have a CDR-GS of 0.5 or 1.0 • Have an RBANS score of 85 or lower indicative of objective cognitive impairment (based upon the DMI score). 8. The participant must be in good health, apart from a clinical diagnosis of early Alzheimer’s disease, as determined by the Investigator based on medical history and screening assessments. 9. The participant must consent to ApoE genotyping.. 10. The participant must have 1 informant/care partner who, in the Investigator’s opinion, has frequent and sufficient contact with the participant (at least 10 hours/week in person or by phone) as to be able to provide accurate information about the participant’s cognitive and functional abilities over time. The informant/care partner ideally has known the participant prior to their cognitive decline to have a reference point for change across time. The informant/care partner must be available by phone to provide information to the Investigator and study staff about the participant as well as agree to attend in-person clinic visits that require partner input for scale completion. The informant/care partner must be literate and provide informed consent and should be available for the duration of the study. The same informant/care partner is required to be consistent across all study visits except under rare, unavoidable circumstances (e.g., unexpected informant health crisis) that are approved by the Investigator and Sponsor.

1. Any uncontrolled medical or neurological/neurodegenerative condition (other than Alzheimer’s disease) that, in the opinion of the Investigator, might be a contributing cause of the participant’s cognitive impairment (e.g., Lewy body dementia, head trauma, substance abuse, frontotemporal dementia, vitamin B12 deficiency, abnormal thyroid function, stroke, or other cerebrovascular condition). 2. Clinically significant and/or unstable psychiatric illness within 6 months prior to Screening. 3. Any documented prior history of chronic schizophrenia. 4. History of long-term major depression or bipolar affective disorder with an active episode in the past 5 years. 5. Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year prior to Screening. 6. Brain MRI performed at Screening (per centrally read MRI) that shows evidence of any of the following: • Acute or subacute haemorrhage • Prior cerebral haemorrhage > 1 cm in diameter on T2* sequence or prior subarachnoid haemorrhage unless it can be documented that the finding is not due to an underlying structural or vascular abnormality (i.e., finding does not suggest participant is at risk of recurrent haemorrhage) • 4 or more microhaemorrhages (defined as ≤ 1 cm in diameter on T2* sequence) • 1 or more localized superficial siderosis findings • Cortical infarct (defined as > 1.5 cm in diameter irrespective of anatomic location) • > 1 lacunar infarct (defined as ≤ 1.5 cm in diameter) • History of diffuse white matter disease as defined by a score of 3 on the age related white matter changes scale • Any finding that, in the opinion of the Investigator, might be a to an underlying structural or vascular abnormality (i.e., finding does not suggest participant is at risk of recurrent haemorrhage) • 4 or more microhaemorrhages (defined as ≤ 1 cm in diameter on T2* sequence) • 1 or more localized superficial siderosis findings • Cortical infarct (defined as > 1.5 cm in diameter irrespective of anatomic location) • > 1 lacunar infarct (defined as ≤ 1.5 cm in diameter) • History of diffuse white matter disease as defined by a score of 3 on the age-related white matter changes scale [Wahlund 2001] • Any finding that, in the opinion of the Investigator, might be a contributing cause of participant’s dementia, might pose a risk to the participant, or might prevent a satisfactory MRI assessment for safety monitoring. 7. History of bleeding disorder or predisposing conditions, blood clotting, or clinically significant abnormal results on coagulation profile at Screening as determined by the Investigator. 8. Presence of diabetes mellitus that, in the judgment of the Investigator, cannot be controlled or adequately managed. 9. History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening. 10. Clinically significant 12-lead ECG abnormalities as determined by the Investigator. 11. Uncontrolled hypertension defined as: average of 3 SBP/DBP readings > 165 mmHg and/or > 100 mmHg at Screening (blood pressure measurements exceeding these limits may be repeated as warranted by the Investigator, but values must be within the specified limits for the participant to be eligible for the study); or persistent SBP/DBP readings > 180 mmHg and/or > 100 mmHg 3 months prior to randomization (Day 1) that, in the opinion of the Investigator, are indicative of chronic uncontrolled hypertension. 12. History of malignancy or carcinoma. The following exceptions may be made after discussion with the Sponsor: • Participants with cancers in remission ≥ 5 years prior to Screening Visit 1. • Participants with a history of excised or treated basal cell or squamous carcinoma of the skin.