Alzheimer's disease (AD) is a progressive neurodegenerative disease and a major global healthcare burden. Currently, the disease is only treated symptomatically and an effective disease-modifying therapy (DMT) that may slow the disease progression, and prevent cognitive and functional deterioration, is yet to emerge. Glucagon-like peptide-1 (GLP-1) analogues are being studied to treat neurodegenerative diseases, due to evidence of their neuroprotective effects in mouse models of AD. This study investigates Semaglutide, a modified human GLP-1RA in Alzheimer's disease to understand the mechanism of the disease. The primary objective of this study is to evaluate the safety and tolerability of oral semaglutide in individuals with mild AD. Moreover, the secondary objective of the study is to evaluate the change in synaptic density using PET before and after treatment with semaglutide.

Inclusion Criteria:

1. Capable of giving and capacity to give informed consent.
2. An individual who can act as a reliable study partner with regular contact
3. Diagnosis of Alzheimer's disease according to the revised NIA-AA criteria
4. Age from 50 years
5. Mini-Mental State Examination (MMSE) score of ≥18; likely complete all the assessments
6. Rosen Modified Hachinski Ischemic score ≤4
7. On stable medication for 2 months before the screening visit; on or off cholinesterase inhibitors
8. Fluency in English and evidence of adequate premorbid intellectual functioning
9. Likely to be able to participate in all scheduled evaluations and complete all required tests

Exclusion Criteria:

1. Any contraindications to the use of oral semaglutide
2. Significant neurological disease other than AD that may affect cognition
3. MRI/CT showing unambiguous aetiological evidence of cerebrovascular disease with regard to their dementia or vascular dementia fulfilling NINCDSAIREN criteria
4. Current presence of a clinically significant major psychiatric disorder
5. Current clinically significant systemic illness that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study
6. Myocardial infarction within the last 1 year
7. Other clinically significant abnormality on physical, neurological or laboratory examination that could compromise the study or be detrimental to the subject
8. History of alcohol or drug dependence within the last 2 years
9. Current use of narcotic medications which could affect cognition. Subjects on anticoagulants will be allowed, but will not have an arterial line inserted
10. Women of childbearing potential. Women who could become pregnant will be required to use adequate contraception throughout the trial. Please see appendix A for more information. All women of childbearing potential will take a pregnancy test before the PET scan.
11. Any contraindications to MRI scanning
12. Any historical evidence of pancreatitis or gallstones as proven by ultrasound or medical admission.
13. History of medullary thyroid cancer
14. Patients diagnosed with T2DM who are unwilling to change their treatment to semaglutide.