A Study of a Potential Disease Modifying Treatment in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation

Inclusion Criteria:

1. Provide written informed consent, signed, and dated by the participant and studypartner, or by the participant's legally authorized representative if applicable,according to local regulations for the ICF and, if applicable, country specificICFs.

2. Participant is at least 18 years old.

3. People of childbearing potential

4. Must have a negative serum pregnancy test at screening (V1)

5. Must agree not to try to become pregnant during the study until 5 half-livesafter the last dose of any study drug.

6. Must agree not to breastfeed from the time of signed ICF until 5 half-livesafter the last dose of any study drug.

7. If partner is not sterilized, must agree to use highly effective contraceptivemeasures from screening (V1) until 5 half lives after last dose of any studydrug

8. Mutation Status:

9. Participant is a carrier of a mutation in an APP, PSEN1, or PSEN2 gene that isassociated with DIAD or does not know their mutation status and there is amutation in their family pedigree that puts them at a direct risk of inheritingthe known mutation;

10. Participant is -25 to -11 years from predicted age of cognitive symptom onsetbased on their mutation type or family pedigree Note: If the at-risk parent isdeemed a non-carrier through confirmed genetic testing at any time during thestudy, the participant will be withdrawn.

11. Cognitive status of participant is normal (CDR-SB 0).

12. Fluency in DIAN-TU trial approved language and evidence of adequate premorbidintellectual functioning. Participants must be fluent in languages for whichcognitive and clinical measures have been translated and validated for use in theDIAN-TU. Fluency is generally defined as daily or frequent functional use of alanguage generally from birth or a young age. In cultures where multiple languagesare spoken or for participants who are multilingual, determination as to whether aparticipant's level of fluency in languages for which clinical and cognitivemeasures are available meets qualification for the study should be made by the sitePI.

13. Participant has adequate visual and auditory abilities to perform all aspects of thecognitive and clinical assessments.

14. Participant is receiving stable doses of medication(s) for the treatment ofnon-excluded medical condition(s) for at least 30 days prior to baseline visit (V2)except for medications taken for episodic conditions (e.g., migraine abortivetherapy, antibiotics, and other medications for upper respiratory andgastrointestinal ailments).

15. Participant has a study partner who in the PI's judgment can provide accurateinformation as to the participant's cognitive and functional abilities, who agreesto provide information at the study visits that require study partner input forscale completion, and who signs the necessary ICF, if applicable.

16. The participant agrees not to donate blood or blood products for transfusion fromthe time of Screening (V1) for a study drug arm, for the duration of the study, andfor 5 half lives after the final dose of study drug.

17. In the opinion of the PI, the participant will be compliant and have a highprobability of completing the study.

18. The participant is able and willing to complete all study-related testing,evaluations, and procedures.

Exclusion Criteria:

1. Significant neurologic disease (other than AD) or psychiatric disease that maycurrently or during the study affect cognition or the participant's ability tocomplete the study. This would include disorders such as: recent or severe headtrauma causing cognitive change, seizure disorder, neurodegenerative disease otherthan DIAD, hydrocephalus, cerebral/spinal hematoma, inflammatory disease, CNSinfection (e.g., encephalitis or meningitis), neoplasm, toxic exposure, metabolicdisorder (including hypoxic or hypoglycemic episodes) or endocrine disorder;psychiatric disorders such as schizophrenia, schizoaffective disorder, bipolardisorder or major depression, or any other psychiatric condition/disorder whichcould significantly interfere with the participant's cooperative participation (e.g., prominent anxiety, agitation or behavioral problems). Disorders that arecontrolled medically or remote history of these disorders (e.g., history of febrileseizures in childhood) that are not likely to interfere with cognitive function andcompliance with study procedures are not exclusionary.

2. At high risk for suicide, e.g., significant suicidal ideation or attempt within last 12 months, current major depression (as defined in Diagnostic and Statistical Manualof Mental Disorders, Fifth Edition [DSM-V]), or increased suicide risk based onscreening Columbia Suicide Severity Rating Scale (C-SSRS). Current stable milddepression or current use of antidepressant medications are not exclusionary.

3. History of clinically evident stroke or history of clinically important carotid orvertebrobasilar stenosis, plaque, or other prominent risk factor for stroke orcerebral hemorrhage (including atrial fibrillation and anticoagulation, documentedtransient ischemic attack [TIA] in the last 12 months) that may be interfering withcognition or is likely to impact with the participant's ability to complete thestudy. Low dose aspirin (≤ 325 mg daily) is not exclusionary.

4. Alcohol or substance use sufficient to meet DSM-V criteria currently or within thepast year.

5. History of or Baseline (V2) visit brain MRI scan indicative of any other significantabnormality, definite microhemorrhages, evidence of a cerebral contusion,encephalomalacia, or aneurysms. Minor or clinically insignificant imaging findingsare not exclusionary.

6. Presence of certain implanted medical devices, such as some pacemakers, aneurysmclips, artificial heart valves, ear implants, or foreign metal objects in the eyes,skin, or body which would preclude MRI scan.

7. Cardiovascular complications such as uncontrolled hypertension, history ofmyocardial infarcts, heart failure, atrial fibrillation, long QT interval on ECGlikely to interfere with participation in or analysis of the trial in the opinion ofthe investigator

8. Hepatic or renal abnormalities that in the opinion of the investigator wouldinterfere with participation in or analysis of the trial.

9. History of Human Immunodeficiency Virus (HIV) infection, history of Hepatitis Binfection within the past year, history of Hepatitis C infection which has not beenadequately treated, history of spirochete infection (e.g., syphilis, Lyme) of theCNS or history of other infection with high risk for interfering with participationor interpretation of the study in the opinion of the investigator.

10. History of clinically significant multiple or severe drug allergies, significantatopy, or severe post-treatment hypersensitivity reactions (including but notlimited to erythema multiforme major, linear IgA dermatosis, toxic epidermalnecrolysis, and/or exfoliative dermatitis) or sensitivity to study-drug specific PETimaging agents with a high risk for interfering with participation or interpretationof the study in the opinion of the investigator.

11. Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within 90 days prior to Baseline (V2) visit (topical and nasal corticosteroids and inhaledcorticosteroids for asthma are permitted) or chemotherapeutic agents for malignancywithin the last 3 years.

12. Current clinically significant abnormalities of thyroid function, or clinicallysignificant deficiency in vitamin B12. Vitamin B12 less than the lower limits ofnormal with normal methylmalonic acid (MMA)/homocysteine is not deemed clinicallysignificant, therefore not exclusionary.

13. Unstable or poorly controlled diabetes which the investigator believes may interferewith participation in or analysis of the study protocol. Participants may berescreened after 3 months to allow optimization of diabetic control

14. Morbid obesity with significant comorbidities or that would preclude MRI imaging.

15. Current use of anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, orapixaban). Daily use of low dose (< 325 mg) aspirin is not exclusionary.

16. Have been exposed to a monoclonal antibody targeting Aβ peptide within the past 6months or 5 half-lives from screening, whichever is longer.

17. Received any other investigational pharmacological treatment within 3 months ofScreening or 5 half-lives, whichever is longer. Note: Use of approved treatments for AD and other medications may be permitted inthis study.

18. Lack of sufficient venous access.

19. Clinically relevant abnormalities in hematology, coagulation, or clinical chemistry.

20. History of cancer that the investigator believes has high risk of recurrence andimpacting study participation or analysis.

21. Any other medical condition that could be expected to progress, recur, or change tosuch an extent that it could bias the assessment of the clinical or mental status ofthe participant to a significant degree or put the participant at special risk.

22. Currently, or within the last month prior to screening, participated in a clinicalstudy, including a nonpharmacological study, without prior approval.

23. Participants with the "Dutch" APP E693Q mutation.

24. Unable to complete baseline visit (V2) procedures with appropriate cognitive andclinical scores for eligibility

25. A centrally read MRI demonstrating presence of ARIA-E, > 4 cerebralmicrohemorrhages, any superficial siderosis, any macrohemorrhage, or severe whitematter disease at screening.

26. Exposure to lecanemab, donanemab, or other investigational amyloid lowering agentswithin the past 6 months or five half-lives from screening, whichever is longer. Note: Use of approved treatments for AD and other medications may be permitted.

27. Investigator site personnel directly affiliated with this trial and/or theirimmediate families, defined as a spouse, parent, child, or sibling, whetherbiological or legally adopted

28. Lilly employees or employees of a third-party organization (TPO) involved in thisstudy that requires exclusion of their employees or have study partners who areLilly employees or are employees of TPOs involved in this study that requireexclusion of their employees