A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants With Early Alzheimer's Disease

Inclusion Criteria

• Male or female with age from 50 and up to 75 years old inclusive.
• 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.
• Mini Mental State Examination (MMSE) score of 22 or above.
• Abnormal level of CSF Abeta amyloid 42 (Aß42) consistent with AD pathology at screening.
• 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.
• Subjects cared for by a reliable informant or caregiver to assure compliance, assist with clinical assessments and report safety issues.
• Women must be post-menopausal for at least one year and/or surgically sterilized.
• Subjects who in the opinion of the investigator is able to understand and provide written informed consent.
• 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

• 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.
• 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.
• 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.
• Concomitant participation in any other clinical trial using experimental or approved medications or therapies.
• 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.
• Current or past history of auto-immune disease, or clinical symptoms consistent with the presence of auto-immune disease.
• 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.
• History of severe allergic reaction (e.g., anaphylaxis) including but not limited to severe allergic reaction to previous vaccines and/or medications.
• Prior history of clinically significant hypoglycaemic episodes.
• 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.
• 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.
• Any clinically significant medical condition likely to impact the immune system (e.g, any history of acquired or innate immune system disorder).
• Use of hydralazine, procainamide, quinidine, isoniazide, TNF-inhibitors, minocycline within the last 12 months prior to screening.
• Use of diltiazem unless on a stable dose for at least 3 months prior to screening.
• 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.
• Concomitant psychiatric or neurologic disorder other than those considered to be related to AD.
• History or presence of uncontrolled seizures.
• History of meningoencephalitis within the past 10 years prior to screening.
• Subjects with a history of h