<h3>Objective:</h3> We aim to evaluate efficacy, safety, and pharmacokinetics/pharmacodynamics of gantenerumab in amyloid-positive participants with early symptomatic Alzheimer’s disease ([AD]; ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) in historically underrepresented populations. Gantenerumab is a fully human anti-amyloid antibody currently being evaluated in two phase III trials (GRADUATE I and II). <h3>Background:</h3> Historic underrepresentation of many racial/ethnic groups in AD clinical trials limits our understanding of AD and hinders data generalizability. <h3>Design/Methods:</h3> ALUMNI AD, a Phase IIIb, multisite, single-arm, open-label US-based study, will evaluate gantenerumab over a 2-year treatment period and 2-year extension. Sites will be distributed across the US based on local AD prevalence and racial/ethnic demographics, and providers’ experience/engagement providing care in diverse communities. Key eligibility criteria include self-reported race/ethnicity as Black/African American, Hispanic/Latinx, American Indian/Alaska Native, Asian American, or Native Hawaiian or Other Pacific Islander; early symptomatic AD diagnosis; age 50–90 years; evidence of amyloid-beta pathology (measured by amyloid positron emission tomography [PET]); and a reliable study partner/partners. Eligibility assessments include the Quick Dementia Rating System and Mini Mental State Examination. The primary endpoint is change from baseline to Week 104 in brain amyloid load (PET). Secondary and exploratory endpoints include changes in additional AD biomarkers (eg, tau), safety assessments, and cognitive and functional outcomes. <h3>Results:</h3> Planned enrollment is approximately 200 participants from up to 40 US sites. The study is expected to start in the first quarter of 2023 pending supportive data from the GRADUATE program, which will be available in the fourth quarter of 2022. <h3>Conclusions:</h3> This study will further our understanding of gantenerumab in historically underrepresented populations who are disproportionately impacted by AD and have been historically excluded from clinical trials. <b>Disclosure:</b> Sheila Seleri has received personal compensation for serving as an employee of Genentech, a member of the Roche group. Sheila Seleri has received stock or an ownership interest from Genentech, a member of the Roche group. Dr. Brangman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Brangman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech-Roche. Dr. Brangman has received personal compensation in the range of $0-$499 for serving as a Consultant for Acadia. Dr. Brangman has received personal compensation in the range of $0-$499 for serving as a Consultant for Eisai. Dr. Brangman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Brangman has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for Columbian Financial Group. Dr. Brangman has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various Legal Firms. The institution of Dr. Brangman has received research support from National Institute on Aging. The institution of Dr. Brangman has received research support from NYS Health Foundation. The institution of Dr. Brangman has received research support from American Geriatrics Society. Dr. Henderson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Henderson has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for International Association for Indigenous Aging. Dr. Henderson has received publishing royalties from a publication relating to health care. Dr. Parker has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. The institution of Dr. Parker has received research support from NIH. Dr. Parker has received personal compensation in the range of $500-$4,999 for serving as a Patient Engagement Advisory Committee with FDA. Ms. Monroe has received personal compensation for serving as an employee of UsAgainstAlzheimer’s. Ms. Monroe has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with University of Southern California. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AARP - Global Council on Brain Health. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AARP - "Staying Sharp" Scientific Advisory Board. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ACADIA. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech (affiliate of F. Hoffmann-La Roche Ltd). Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Health and Wellness Partners, LLC. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ironshore Pharmaceuticals. Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving as a Consultant for Praxis Bioresearch. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sygnature Discovery. Jacobo E. Mintzer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AARP - "Staying Sharp" Scientific Advisory Board. Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Study Title: NAB-It: Nabilone for Agitation Blinded Intervention Trial. Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Study Title: WeCareAdvisory Study. Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Technology Accelerator Company (TAC). Jacobo E. Mintzer has stock in Biopharma Connex. Jacobo E. Mintzer has stock in NeuroQuest. Jacobo E. Mintzer has stock in Recruitment Partners. The institution of Jacobo E. Mintzer has received research support from Eisai Inc.. The institution of Jacobo E. Mintzer has received research support from Alzheimer’s Clinical Trials Consortium. The institution of Jacobo E. Mintzer has received research support from Eli Lilly and Company. The institution of Jacobo E. Mintzer has received research support from Alzheimer’s Therapeutic Research Institute. The institution of Jacobo E. Mintzer has received research support from JHSPH Center for Clinical Trials. Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving as a Steering Committee Member with Alzheimer’s Clinical Trials Consortium (ACTC). Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving as a Steering Committee Member with Alzheimer’s Disease Cooperative Study (ADCS). Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving as a Steering Committee Member with Elder Court. Jacobo E. Mintzer has received personal compensation in the range of $0-$499 for serving as a Unpaid Consultant/Association Member with International Psychogeriatric Association (IPA). Dr. Wise-Brown has received personal compensation for serving as an employee of Genentech. Dr. Grundman has received personal compensation for serving as an employee of Global R&D Partners. Dr. Smith has received personal compensation for serving as an employee of Roche Products Ltd. Dr. Smith has stock in Hoffman La Roche. Rachelle Doody has nothing to disclose. Dr. Lin has received personal compensation for serving as an employee of Genentech. Dr. Lin has stock in Genentech. Beverly Assman has nothing to disclose. Dr. Rippon has received personal compensation for serving as an employee of Genentech. Dr. Rippon has stock in Genentech.