AZD0530 is an inhibitor of Src and Abl family kinases1. It has been developed as treatment for malignancies because these kinases play a role in tumor invasion and proliferation. However, the Src family kinases (SFKs) are highly expressed in brain and have major effects on synaptic plasticity2. Moreover, the investigators have recently shown that a specific SFK, namely Fyn, is aberrantly activated by specific conformations of the Amyloid Beta (Aß) peptide from Alzheimer's disease (AD). Genetic deletion of Fyn rescues AD deficits in preclinical models. This clinical trial will test the potential benefit of AZD0530 for Alzheimer's disease modification.

Inclusion Criteria

1. NIA-Alzheimer's Association core clinical criteria for probable AD

2. 18F-Florbetapir scan with evidence of elevated Aβ (based on central review)

3. Age between 55-85 (inclusive)

4. MMSE score between 18 and 26 (inclusive)

5. Stability of permitted medications for 4 weeks. In particular:

   • Stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
   • Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen

6. Geriatric Depression Scale less than 6 [Note: a score ≥6 on this screening scale may be permissible, if the subject is examined by a site clinician and judged not to be depressed.]

7. Study partner is available who has frequent contact with the subject (e.g., average of 10 hours per week or more), and can accompany the subject to most visits to answer questions about the subject

8. Visual and auditory acuity adequate for neuropsychological testing

9. Good general health with no disease expected to interfere with the study

10. Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile)

11. Modified Hachinski less than or equal to 4

12. Completed six grades of education or has a good work history

13. Must speak English or Spanish fluently

Exclusion Criteria

1. Any significant neurologic disease other than AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities

2. Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure

3. Subjects that have any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or cardiac pacemaker

4. Major depression, bipolar disorder as described in DSM-IV within the past 1 year or psychotic features, agitation or behavioral problems within 3 months, which could lead to difficulty complying with the protocol

5. History of schizophrenia (DSM V criteria)

6. History of alcohol or substance abuse or dependence within the past 2 years (DSM V criteria)

7. Clinically significant or unstable medical condition, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic disease in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results, or the subject's ability to participate in the study.

8. Has had a history within the last 5 years of a primary or recurrent malignant disease with the exception of non-melanoma skin cancers, resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with normal prostate-specific antigen post-treatment

9. Clinically significant abnormalities in B12 or TFTs that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.

10. Residence in skilled nursing facility.

11. Use of any excluded medication as described in study protocol

12. Current or recent participation in any procedures involving radioactive agents, including current, past, or anticipated exposure to radiation in the workplace, such that the total radiation dose exposure to the subject in a given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1. This guideline is an effective dose of 5 rem received per year.

13. Neutropenia defined as absolute neutrophils count of <1,800/microliter

14. Thrombocytopenia defined as platelet count <120x103/microliter

15. For CSF sub-study participants, a current blood clotting or bleeding disorder, or significantly abnormal PT or PTT at screening

16. Clinically significant abnormalities in screening laboratories, including:

    • Aspartate aminotransferase (AST) >1.5 times ULN
    • Alanine aminotransferase (ALT) > 1.5 times ULN
    • Total bilirubin >1.5 times ULN
    • Serum creatinine >2.0 times ULN

17. History of interstitial lung disease

18. Patients whom the PI deems to be otherwise ineligible