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

The investigators hypothesize that Nilotinib will be safe in individuals with mild to moderate AD. Specifically, investigators hypothesize that low daily oral doses of Nilotinib will lead to CSF penetration, CNS Abl inhibition, and stabilization of CSF total Tau and p-Tau231/181 and Abeta42/40 levels. The investigators hypothesize that Nilotinib will decrease brain load of amyloid using amyloid positron emission tomography (PET). The investigators also predict that Nilotinib will reduce CSF markers of cell death, including neuron specific enolase (NSE) and S100B.

Inclusion Criteria: 1. Age ≥ 50 2. Fluent in English 3. Biomarker confirmed AD with CSF level of Abeta42 \ 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 mental retardation 18. Stable use of cholinesterase inhibitors and memantine (U.S. FDA-approved medications for 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 screening is allowed. 19. Clinical laboratory values within normal limits or, if abnormal, must be judged to be clinically insignificant by the investigator Exclusion Criteria: 1. Non-AD dementia, probable AD with Down syndrome, APP, PS-1, or PS-2 mutations (known familial 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, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance 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 of cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia 7. Prescribed strong CYP3A4 inhibitors or a medical history of liver or pancreatic disease 8. Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory 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 stable prostate cancer are not exclusionary) 10. Pregnancy or possible pregnancy 11. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets \< 100,000, use of Coumadin/warfarin, or history of a bleeding disorder 12. Contraindication to MRI 13. Evidence of more than 4 micro hemorrhages and/or hemosiderosis by a recent (12 months) and/or the screening MRI. 14. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant. 15. Enrolled in another active trial investigating an experimental drug or therapy for AD 16. HIV positive