Safety and Tolerability of AZD0530 (Saracatinib) in Alzheimer's Disease

Inclusion Criteria:

1. NIA-Alzheimer's Association core clinical criteria for probable AD 2. Age between 50-90
(inclusive). 3. MMSE score between 16 and 26 (inclusive) 4. Clinical Dementia Rating =
0.5, 1.0, or 2 5. Stability of permitted medications for 4 weeks. In particular, subjects
may:

1. Take stable doses of antidepressants (if they are not currently depressed or do not
have a history of major depression within the past 1 year).

2. Washout from psychoactive medication for at least 4 weeks prior to screening.

3. Cholinesterase inhibitors are allowable if stable for 12 weeks prior to screen. 6.
Geriatric Depression Scale less than 6. 7. Study partner is available who has
frequent contact with the subject (e.g. an average of 8 hours per week or more), and
can accompany the subject to all clinic visits for the duration of the protocol.

8. Visual and auditory acuity adequate for neuropsychological testing. 9. Good
general health with no diseases 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 (sufficient to exclude mental retardation).

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. Subjects with multiple lacunes or lacunes in a critical memory
structure are excluded.

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

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

5. History of schizophrenia (DSM IV criteria).

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

7. Any significant systemic illness or unstable medical condition, which could lead
to difficulty complying with the protocol.

8. Clinically significant abnormalities in B12 or TFTs that might interfere with
the study.

9. Residence in skilled nursing facility.

10. Current use (within 30 days of screening) of specific psychoactive medications
(e.g., typical neuroleptics, narcotic analgesics, antiparkinsonian medications,
systemic corticosteroids, or medications with significant central
anticholinergic activity, etc.). Current use of warfarin.

11. Investigational amyloid lowering therapies are prohibited two months prior to
screening and for the duration of the trial. Other investigational agents are
prohibited one month prior to screening and for the duration of the trial.

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.

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 patient at risk because of participation in the study, or influence
the results, or the patient's ability to participate in the study.

8. Clinically significant abnormalities in B12 or TFTs that might interfere with the
study.

9. Residence in skilled nursing facility. 10. Current use (within 30 days of
screening) of specific psychoactive medications (e.g., typical neuroleptics, narcotic
analgesics, antiparkinsonian medications, systemic corticosteroids, or medications
with significant central anticholinergic activity, etc.). Current use of warfarin.

11. Investigational amyloid lowering therapies are prohibited two months prior to
screening and for the duration of the trial. Other investigational agents are
prohibited one month prior to screening and for the duration of the trial.

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. Current use (within 30 days of screening and throughout the protocol including
the 2 week follow-up period) of the following medications: a) strong CYP3A4
inhibitors including: atazanavir, indinavir, ritonavir, saquinavir, nelfinavir,
ketoconazole, itraconazole, clarithromycin, telithromycin, and nefazodone; b) strong
CYP3A4 including: rifampicin, phenytoin, phenobarbital, and carbamazepine; c) certain
CYP3A4 substrates including colchicine, cyclosporine, disopyramide, fluticasone,
quinidine, vinblastine, vincristine. Patients taking sildenafil, tadalafil, and
vardenafil will be advised to stop taking these medications for the duration of the
trial.

14. Neutropenia defined as absolute neutrophils count of <1,500/microliter. 15.
Thrombocytopenia defined as platelet count <100x103/microliter. 16. Current blood
clotting or bleeding disorder, or significantly abnormal PT or PTT at screening.

17. 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.

18. History of interstitial lung disease.