Impact of Nilotinib on Safety, Biomarkers and Clinical Outcomes in Mild to Moderate Alzheimer's Disease

Inclusion Criteria:

1. Age ≥ 50

2. Fluent in English

3. Biomarker confirmed AD with CSF level of Abeta42 <600ng/mL

4. Able to ingest oral medications

5. Diagnosis of mild to moderate AD according to dementia criteria outlined by McKhannet al.

6. Neuroimaging (MRI or CT) consistent with the diagnosis of AD within the past year

7. MMSE between 17 and 24 (inclusive) at screening

8. Modified Hachinski score ≤ 4

9. QTc interval 350-460ms, inclusive

10. Caregiver/study partner to accompany participant to all visits and have directcontact with the participant > 2 days/week

11. Written informed consent

12. Capability and willingness to comply with all study criteria

13. Supervision available for study medication

14. Stable medical conditions for 3 months prior to screening visit

15. Stable medications for 4 weeks prior to screening visit

16. Able to complete baseline assessments

17. Minimum of 6 years of education, or work history sufficient to exclude mentalretardation

18. Stable use of cholinesterase inhibitors and memantine (U.S. FDA-approved medicationsfor patients with probable AD), vitamin E (up to 400 IU daily), estrogens, aspirin (81-300 mg daily), and cholesterol-lowering agents for 3 months prior to screeningis allowed.

19. Clinical laboratory values within normal limits or, if abnormal, must be judged tobe clinically insignificant by the investigator

Exclusion Criteria:

1. Non-AD dementia, probable AD with Down syndrome, APP, PS-1, or PS-2 mutations (knownfamilial AD), LBD and Fronto-temporal dementia (FTD)

2. History of clinically significant stroke

3. Current evidence or history in past two years of epilepsy, focal brain lesion, headinjury with loss of consciousness or DSM-IV criteria for any major psychiatricdisorder including psychosis, major depression, bipolar disorder, alcohol orsubstance abuse

4. Sensory impairment that would preclude participation/cooperation with the protocol

5. Patients with hypokalemia, hypomagnesaemia, or long QTc syndrome.

6. Concomitant drugs known to prolong the QTc interval (>461ms) and history ofcardiovascular disease, including myocardial infarction or cardiac failure, angina,arrhythmia

7. Prescribed strong CYP3A4 inhibitors or a medical history of liver or pancreaticdisease

8. Evidence of any significant clinical disorder or laboratory finding that renders theparticipant unsuitable for receiving an investigational drug including clinicallysignificant or unstable hematologic, hepatic, cardiovascular, pulmonary,gastrointestinal, endocrine, metabolic, renal or other systemic disease orlaboratory abnormality

9. Active neoplastic disease, history of cancer five years prior to screening,including breast cancer (history of treated basal or squamous skin cancer, or stableprostate cancer are not exclusionary)

10. Pregnancy or possible pregnancy

11. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative jointdisease or deformity of the spine, platelets < 100,000, use of Coumadin/warfarin, orhistory of a bleeding disorder

12. Contraindication to MRI

13. Evidence of more than 4 micro hemorrhages and/or hemosiderosis by a recent (12months) and/or the screening MRI.

14. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) andmethylmalonic acid (MMA)) indicate that it is not physiologically significant.

15. Enrolled in another active trial investigating an experimental drug or therapy forAD

16. HIV positive