Study to Evaluate the Efficacy and Safety of GSK239512 in Alzheimer's Disease

A subject will be eligible for inclusion in this study only if all of the following criteria apply: * Male or female subjects with a clinical diagnosis of probable Alzheimer's disease in accordance with the NINCDS-ADRDA criteria, with symptoms of AD for at least 3 months. * A Haschinski ischaemia score less than or equal to 4. * Has undergone MRI or CT scan in the last 12 months. (For subjects not meeting this criteria, as scan will be conducted as part of the screening procedures). * The subject has an MMSE score at Screening of 16 to 24 inclusive. * Male or female aged 50 or above, at the time of signing the informed consent. * If female, the subject must be post-menopausal, i.e. 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and estradiol less than 40 pg/ml (\<140 pmol/L) is confirmatory\] or surgically sterile (documented tubal ligation or hysterectomy). \[Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.\] * Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of study medication. * The subject has the ability to comply with the study procedures as judged by the investigator. * Subject lives with (or has substantial periods of contact with) a permanent caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status. A permanent caregiver is one who is able to provide care to the subject for the duration of the study without interruption for more than 1 week at a time. If at times during the study the permanent caregiver is unable to look after the subject, this period of absence of the caregiver must be covered by another caregiver. A permanent caregiver need not be living in the same residence with the subject. For such a caregiver, the investigator has to be satisfied that the subject can contact the caregiver readily during the times when the caregiver is not with the subject. If in doubt about whether a subject's care arrangements are suitable for inclusion, the investigator should discuss this with the GSK Medical Monitor. * The subject has provided full written informed consent prior to the performance of any protocol specific procedure, or if unable to provide informed consent due to cognitive status, full written informed consent on behalf of the subject has been provided by a legally acceptable representative. * The caregiver has provided his / her written consent prior to the performance of any protocol specific procedure * AST and ALT less than 2xULN; alkaline phosphatase and bilirubin, less than or equal to 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%). * If the subject is on any prior medications, they should satisfy the requirements in Section 9. A subject will not be eligible for inclusion in this study if any of the following criteria apply: * In the opinion of the investigator, following review of CT/MRI scans in the past 12 months and completion of neurological review there could be other probable causes of dementia which include, but are not limited to: * History and/or evidence (CT or MRI scan performed since the onset of symptoms) of any other CNS disorder that could be interpreted as the primary cause of dementia: e.g. cerebrovascular disease, structural or developmental abnormality, epilepsy, infections, degenerative or inflammatory/demyelinating CNS conditions other than AD. * Clinically significant focal findings on the neurological exam (excluding changes attributable to peripheral nervous system injury). * Abnormal result of vitamin B12 and syphilis serology, where this is thought to be the cause of, or to contribute to the severity of, the subject's dementia. Subjects should be euthyroid based on laboratory results at the screening visit. Subjects maintained on thyroid medication must be euthyroid for a period of 2 months prior to the screening visit. If laboratory values are outside normal limits, but the investigator believes that the thyroid condition is stable and has no impact on cognition, such cases will be decided on case by case basis in discussion with the medical monitor. * Diagnosis of possible, probable or definite vascular dementia in accordance with National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche l'Enseignement en Neurosciences (NINDS-AIREN) criteria. * Prior diagnosis of significant psychiatric illness such as schizophrenia or bipolar affective disorder with current symptoms related to the diagnoses such that in the opinion of the Investigator would interfere with participation in the study, or current depression (a score of greater than or equal to 8 on the Cornell Scale for Depression in Dementia), or subjects with other psychiatric features (including but not limited to having hallucinations) in their AD which in the opinion of the investigator, increase risk to safety. * Subjects, who in the investigator's judgement, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 2 months prior to screening. * History or presence of significant sleep disturbance, such as severe insomnia or sleep disturbance associated with nocturnal wandering, nocturnal confusion / disorientation / agitation, which in the opinion of the investigator, may increase safety risk. * History or presence of known or suspected seizures, unexplained significant loss of consciousness within last 6 months. Subjects who had febrile seizures in childhood may be included if these ceased by age 10 and they have had no other type of seizure in their medical history and have not been on anti-epileptic medications. * History or presence of significant cardiovascular, gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study. * History of alcohol or other substance abuse, according to the Diagnostic and Statistical Manual of Mental Disorders - Substance related disorders (DSM-IV) criteria within 3 years prior to the onset of AD symptoms, or since the onset of AD symptoms. * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Uncontrolled hypertension with systolic BP greater than or equal to 160 and/or diastolic greater than or equal to 95 mmHg. Subjects with controlled hypertension with systolic BP less than 160 mmHg and diastolic less than 95 mmHg for at least 4 weeks are acceptable. * Systolic BP less than 100 mmHg and/or diastolic less than 60 mmHg. * Subjects with a QTcB and/or QTcF of greater than 450ms or greater than 480ms if they have bundle branch block or other ECG abnormalities which, in the opinion of the investigator is clinically significant in that they may increase safety risk. * The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. * Pregnant females as determined by positive urine human chorionic gonadotropin (hCG) test at screening or prior to dosing. * Treatment with cholinesterase inhibitors (including Tacrine), memantine or selegiline within the last 3 months prior to screening. No patients with AD who are already on these medications at the time of screening will be recruited, as it would be unethical to withdraw these medications for study participation. Only AD subjects who are not yet on these medications, or who have withdrawn from these medications for other reasons previously, may be enrolled into this study. * Use of the following medications within the last 30 days or 5 half-lives of these medications from screening (prohibited in Section 9.2): * Any other treatments approved in the countries for treatment of cognitive symptoms of AD. * Anti-psychotic drugs (typical or atypical dopaminergic antagonists or modulators). * Any CNS stimulants (e.g., modafinil). * Mood stabilization drugs (e.g. lithium, valproate, cabamazepine). * Barbiturates, MAO inhibitors, Gingko biloba and other herbal treatments for cognitive impairment. * Potent P-glycoprotein inhibitors (e.g. itraconazole, ketoconazole, cyclosporin, loperamide, diltiazem, verapamil, spironolactone, quinidine, bepridil, quinine, carvedilol). * Known potent inhibitors or inducers of the CYP3A4 enzyme (e.g., verapamil, ketoconazole, cimetidine, rifampin, modafinil). * Anti-cholinergic drugs or drugs which have anti-cholinergic effects (e.g. amitriptyline, amantidine). * Anti-histamines which are CNS penetrant. * Chronic sedative medications (greater than or equal to 4 days per week for the past 4 weeks prior to screening). * Any other investigational drug. * Use of other prescription or non-prescription drugs, including herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety, or are permitted under Section 9). * Subjects who plan to commence treatment with prohibited medications in Section 9.2. * Consumption of red wine, seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until the follow-up visit. * Subjects who have commenced or are already undertaking a cognitive rehabilitation programme within 1 month of screening. Subjects who have stopped their cognitive rehabilitation programme at least 1 month prior to screening need not be excluded if they satisfy other eligibility criteria. * Unwillingness or inability to follow the procedures outlined in the protocol. * Subject or caregiver is an immediate family member or employee of the participating Investigator, any of the participating site staff or GSK staff.