This study is a multicenter, double blind, randomized, placebo-controlled study to evaluate the safety, tolerability and immunogenicity of different doses, regimens and combinations of Tau targeted vaccines in participants with early Alzheimer's Disease.

Inclusion Criteria:

1. Male or female with age from 50 and up to 75 years old inclusive.
2. Mild Cognitive Impairment (MCI) due to AD or Mild AD according to NIA-AA criteria and Clinical Dementia Rating scale (CDR) global score of 0.5 or 1 respectively.
3. Mini Mental State Examination (MMSE) score of 22 or above.
4. Abnormal level of CSF Abeta amyloid 42 (Aß42) consistent with AD pathology at screening.
5. Subjects either not taking any marketed treatment for AD or receiving a stable dose of an acetylcholinesterase inhibitor and/or memantine for at least 3 months prior to baseline.
6. Subjects cared for by a reliable informant or caregiver to assure compliance, assist with clinical assessments and report safety issues.
7. Women must be post-menopausal for at least one year and/or surgically sterilized.
8. Subjects who in the opinion of the investigator is able to understand and provide written informed consent.
9. Both subject and informant or caregiver must be fluent in one of the languages of the study and able to comply with all study procedures, including lumbar punctures.

Exclusion criteria:

1. Participation in previous clinical trials for AD and/or for neurological disorders using active immunization unless there is documented evidence that the subject was treated with placebo only and the placebo vaccine is not expected to induce any specific immune response.
2. Participation in previous clinical trials for AD and/or for neurological disorders using any passive immunization within the past 6 months (or 5 half-lives of the investigational antibody, whichever is longer) prior to screening unless there is documented evidence that the subject was treated with placebo only and the placebo is not expected to induce any specific immune response.
3. Participation in previous clinical trials for AD and/or for neurological disorders using any small molecule drug including BACE-1 inhibitors within the past 3 months prior to screening.
4. Concomitant participation in any other clinical trial using experimental or approved medications or therapies.
5. Presence of positive Anti-nuclear Antibody (ANA) titers at a dilution of at least 1:160 in subjects without clinical symptoms of auto-immune disease.
6. Current or past history of auto-immune disease, or clinical symptoms consistent with the presence of auto-immune disease.
7. Immune suppression including but not limited to the use of immunosuppressive drugs or systemic steroids unless they have been prescribed transiently more than 3 months prior to screening.
8. History of severe allergic reaction (e.g., anaphylaxis) including but not limited to severe allergic reaction to previous vaccines and/or medications.
9. Prior history of clinically significant hypoglycaemic episodes.
10. Drug or alcohol abuse or dependence currently met or within the past five years according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria.
11. Any clinically significant medical condition likely to interfere with the evaluation of safety and tolerability of the study treatment and/or the adherence to the full study visit schedule.
12. Any clinically significant medical condition likely to impact the immune system (e.g, any history of acquired or innate immune system disorder).
13. Use of hydralazine, procainamide, quinidine, isoniazide, TNF-inhibitors, minocycline within the last 12 months prior to screening.
14. Use of diltiazem unless on a stable dose for at least 3 months prior to screening.
15. Significant risk of suicide defined, using the Columbia-Suicide Severity Rating Scale, as the subject answering: "yes" to suicidal ideation questions 4 or 5 or answering: "yes" to suicidal behavior within the past 12 months.
16. Concomitant psychiatric or neurologic disorder other than those considered to be related to AD.
17. History or presence of uncontrolled seizures.
18. History of meningoencephalitis within the past 10 years prior to screening.
19. Subjects with a history of hemorrhagic and/or non-hemorrhagic stroke.
20. Presence or history of peripheral neuropathy.
21. History of inflammatory neurological disorders with potential for CNS involvement.
22. Screening MRI scan showing structural evidence of alternative pathology not consistent with AD which could cause the subject's symptoms.
23. MRI examination cannot be done for any reason, including but not limited to metal implants contraindicated for MRI studies and/or severe claustrophobia.
24. Significant hearing or visual impairment or other issues judged relevant by the investigator preventing to comply with the protocol and to perform the outcome measures.
25. Clinically significant infections or major surgical operation within 3 months prior to screening.
26. Any vaccine received within the past 2 weeks before screening, including influenza vaccine.
27. Clinically significant arrhythmias or other clinically significant abnormalities on ECG at screening.
28. Myocardial infarction within one year prior to baseline, unstable angina pectoris, or significant coronary artery disease.
29. History of cancer within the past 5 years other than treated squamous cell carcinoma, basal cell carcinoma and melanoma in situ, or in-situ prostate cancer or in-situ breast cancer which have been fully removed and are considered cured.
30. Clinically significant deviations from normal values for hematologic parameters, liver function tests, and other biochemical measures, that are judged to be clinically significant in the opinion of the investigator.
31. Pregnancy confirmed by blood test at screening, or subject planning to be pregnant or lactating.
32. Receipt of any anticoagulant drug or antiplatelet drug, except aspirin at doses of 100 mg daily or lower.
33. Receipt of any antipsychotic drugs unless on stable low doses for the treatment of insomnia.
34. Donation of blood or blood products within 30 days prior to screening or plans to donate blood while participating in the study.
35. Positive Venereal Disease Research Laboratory (VDRL) consistent with active syphilis at screening.
36. Positive HIV test at screening.
37. Laboratory or clinical evidence of active hepatitis B and/or C at screening.
38. Serum creatinine greater than 1.5x upper limit of normal, abnormal thyroid function tests or clinically significant reduction in serum B12 or folate levels.

Individual participant data (IPD) are not planned to be shared for this early-phase non-pivotal ACI-35-1802 Phase 1b/2a study. However, group-level data may be shared to qualified researchers who engage in rigorous independent scientific research after the review and approval of a proposal sent to the sponsor (see Contacts) and the execution of a data sharing agreement.

In addition, the Clinical Study Protocol and the Statistical Plan will be available in this registry once the study results are released.

Publication shall not be made by PIs before a first multi-site publication by Sponsor. If no multi-site publication is made within 18 months after study completion, PIs can publish under conditions: Prior any publication submission, PI shall send Sponsor any information to be disclosed and Sponsor have 60 days from receipt to review and comment. PI shall remove any Confidential Information and upon Sponsor request further delay publication for up to 120 days to protect Sponsor interests.