Study of AV-1959D, an Amyloid Beta Vaccine

Inclusion Criteria:

1. Male or female subjects from 60 to 85 years of age, both inclusive.

2. Mild cognitive impairment (MCI) due to Alzheimer's disease (AD), according to Albertet al., or mild AD dementia, according to McKhann et al., and must have thefollowing:

• Mini-Mental State Examination (MMSE) score from 22 to 30;

• Clinical Dementia Rating (CDR) global score of 0.5 or 1.0.

3. A positive visual Aβ positron emission tomography (PET) scan. Previously obtainedPET scan (within 24 months of screening) is permissible and must be submitted to thecentral imaging reader to confirm that study inclusion criteria are met.

4. Subjects on approved AD medications (e.g., acetylcholine esterase inhibitors,memantine) are required to be on a stable dose for a minimum 3 months beforebaseline and with no dosage adjustments expected during the study. Continuation ofsubjects with dose adjustments for approved AD medications during the study may beallowed after discussion between the Investigator and the Medical Monitor.

5. The subject has a reliable study partner who will accompany the patient to allclinic visits during the study and, in the Investigator's opinion, has frequent andsufficient contact with the subject as to be able to provide accurate informationabout the subject's cognitive and functional abilities.

6. The subject's sight and hearing (hearing aid permissible) are sufficient forcompliance with the study procedures.

7. Signed informed consent form by the subject and study partner prior to studyparticipation.

Exclusion criteria:

1. Participation in another investigational drug or device study or treated with aninvestigational drug within 30 days or 5 half-lives, whichever is longer, beforedosing.

2. Prior administration of any amyloid-beta or tau immunotherapy (vaccine, antibody)

3. Magnetic resonance imaging (MRI) showing evidence of any of the following:

• More than 1 lacunar infarct greater than 1.5 cm

• Any territorial infarct, including acute or chronic, greater than 1.5 cm

• Subjects who have a combined number of microbleeds and areas of leptomeningealhemosiderosis (i.e., cumulative ARIA-H) on the MRI of > 5 (and should notinclude any disseminated leptomeningeal hemosiderosis)

• Subjects who have a presence of any other significant cerebral abnormalities,including ARIA-E, as assessed in the screening MRI scan.

4. Contraindications for MRI scanning, including implanted metallic devices (e.g.,non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metalpins; surgical clips; or other implanted metal parts), or claustrophobia ordiscomfort in confined spaces.

5. Use of immunomodulatory or growth-stimulating factors such as systemiccorticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody,GM-CSF, C-CSF, interferon (IFN), or interleukin-2 (IL-2) within 30 days prior tostudy entry.

6. Concurrent use of warfarin or other coumarin derivatives or a combination ofacetylsalicylic acid and an anti-platelet agent (e.g., clopidogrel). Low dose ofacetylsalicylic acid (≤81 mg per day) is allowed.

7. Parenteral use of immunoglobulin preparations, blood products, plasma derivatives.

8. Any serious illness requiring systemic treatment and/or hospitalization within 4weeks prior to study entry.

9. Any major or unstable illness, including unstable ischemic cardiovascular disease,or require use of excluded medications.

10. History/evidence of clinically relevant pathology related to cardiovascular system,respiratory tract, gastrointestinal tract, endocrinology, immunology, hematology, orany other systemic disorder/major surgeries that in the opinion of the Investigatorwould confound the subject's participation and follow-up in the clinical study.

11. Subjects with insulin-dependent diabetes.

12. Cardiac arrhythmias or palpitations [e.g., supraventricular tachycardia, atrialfibrillation, frequent ectopy, or sinus bradycardia]. Cardiac conductionabnormalities to be specified including prolonged QT interval and bundle branchblocks.

13. Subjects with pre-existing autoimmune diseases.

14. A medical condition that in the opinion of the Investigator might be a contributingcause of cognitive impairment.

15. History/evidence of severe local or systemic reactions to vaccination or significantallergic reactions.

16. History of seizure disorder.

17. Any other medical, psychological, social condition or diagnostic test which, in theopinion of the Investigator and Medical Monitor may lead to screen failure orprevent the subject from fully participating in the study, represent a concern forstudy compliance, or constitute a safety concern to the subject.