A Study to Evaluate the Efficacy and Safety of Gantenerumab in Participants at Risk for or at the Earliest Stages of Alzheimer's Disease (AD)

Key Inclusion Criteria:

• Willing and able to comply with the study protocol and complete all aspects of thestudy [including cognitive and functional assessments, physical and neurologicalexaminations, MRI, CSF collection, genotyping, and positron emission tomography (PET) imaging].

• Cognitively unimpaired with a screening clinical dementia rating global score (CDR-GS) of 0, and Repeatable Battery for the Assessment of NeuropsychologicalStatus Delayed Memory Index (RBANS DMI) >=80.

• Evidence of cerebral amyloid accumulation.

• Participants who have an available person (referred to as a "study partner").

• Fluent in the language of the tests used at the study site.

• Adequate visual and auditory acuity, sufficient to perform neuropsychologicaltesting (eye glasses and hearing aids are permitted).

• Agreed not to participate in other interventional research studies for the durationof this trial.

• For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive methods that result in a failure rateof <1% per year during the treatment period and for at least 17 weeks after thefinal dose of study treatment.

Key Exclusion Criteria:

• Any evidence of an underlying neurological or neurodegenerative condition that maylead to cognitive impairment other than AD.

• Clinical diagnosis of mild cognitive impairment (MCI), prodromal AD, or any form ofdementia.

• History or presence of intracranial or intracerebral vascular malformations,aneurysm, subarachnoid hemorrhage, or intracerebral macrohemorrhage.

• History or presence of posterior reversible encephalopathy syndrome.

• History of ischemic stroke with clinical symptoms or an acute event that isconsistent with a transient ischemic attack within 12 months of screening.

• History of severe, clinically significant (i.e., resulting in persistent neurologicdeficit or structural brain damage) central nervous system (CNS) trauma (e.g.,cerebral contusion).

• History or presence of intracranial mass lesion (e.g., glioma, meningioma) thatcould potentially impair cognition or lead to progressive neurological deficits.

• Infections that may affect brain function or a history of infections that resultedin neurologic sequelae [e.g., human immunodeficiency virus (HIV), syphilis,neuroborreliosis, and viral or bacterial meningitis and encephalitis].

• History of major depression, schizophrenia, schizoaffective disorder, or bipolardisorder.

• At risk for suicide.

• History of alcohol and/or substance abuse or dependence.

• History or presence of clinically significant systemic vascular disease, atrialfibrillation or heart failure.

• Within the last year, experienced unstable or clinically significant cardiovasculardisease (e.g., myocardial infarction).

• Uncontrolled hypertension.

• Chronic kidney disease, indicated by creatinine clearance <30 mL/min.

• Confirmed and unexplained impaired hepatic function.

• History of, or are known to currently have an HIV infection, or hepatitis B orhepatitis C virus infection that has not been adequately treated.

• History or presence of systemic autoimmune disorders that may lead to progressiveneurological impairment with associated cognitive deficits.

• Systemic immunosuppression or immunomodulation due to the continuing effects ofimmunosuppressant or immunomodulating medications.

• Current COVID-19 infection.

• Evidence of folic acid or vitamin B-12 deficiency.

• Any passive immunotherapy (Ig) or other long-acting biologic agent to prevent orpostpone cognitive decline within 1 year of screening.

• Any other investigational treatment within 5 half-lives or 6 months (whichever islonger) prior to screening.

• Typical/Atypical anti-psychotic medications or neuroleptic medications.

• Anticoagulation medications within 3 months of screening with no plans to initiateany prior to randomization.

• Any previous treatment with cholinesterase inhibitors and N-methyl-D-aspartatereceptor antagonists are exclusionary at screening.

• Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 17 weeks after the final dose of gantenerumab.

• Impaired coagulation.

• Known history of severe allergic, anaphylactic, or other hypersensitivity reactionsto chimeric, human, or humanized antibodies or fusion proteins, includinggantenerumab and gantenerumab excipients.

• Participants who reside in a skilled nursing facility such as a convalescent home orlong-term care facility.

• Participants who require residence in such facilities during the study may continuein the study and be followed for efficacy and safety, provided that they have astudy partner who meets the study partner requirements.