TSPO Modulation in AD

Inclusion criteria

for AD:

• Subjects aged between 60-90 years old
• Male or postmenopausal female
• Fertile men are eligible to participate if they are willing to use the contraception methods listed in the PIS, during treatment and for 90 days after the last dose of treatment
• Able to provide written informed consent prior to any study-mandated procedures
• AA genotype at rs6971 (TSPO) locus
• Clinical diagnosis of AD by dementia specialist, fulfilling NIA-AA criteria
• Mild - moderate cognitive impairment (MMSE = 20-27 )
• AD biomarker positive MCI patients

Inclusion criteria

for HV:

• Subjects aged 18 years or older
• Male or Female
• Female subjects of childbearing potential must be willing to have a pregnancy test before scanning
• Able to provide written informed consent prior to any study-mandated procedures
• Subjects willing to have blood samples collected for genotyping (ApoE and TSPO rs6971)
• AD biomarker positive

Exclusion criteria

for AD:

• History of migraine (with attack frequency greater than 1 per month)
• Clinical history of suggestive of dementia with Lewy Bodies such as REM Sleep Behaviour Disorder
• Conditions affecting safe engagement in the intervention
• Conditions preventing completion of study procedures, e.g. severe loss of vision or hearing
• Clinically significant renal disease (eGFR <60 ml/min per 1.73m2)
• Clinically significant liver disease (abnormal serum transaminases)
• Contraindications to MRI scanning or exposure to gadolinium-based contrast agents
• Change of medications approved for AD (eg. Galantamine, rivastigmine, and donepezil) or antihypertensives within the last 28 days or planned during the timeframe of the study
• Severe respiratory disease with chronic hypoxia (sats <92%), known CO2 retention or need for home oxygen therapy
• Use of the following medications or therapies:
• Severe and moderate P450 CY3A4 inhibitors: Boceprevir, Clarithromycin, Cobicistat, Idelalisib, Itraconazole, Ketoconazole, Nelfinavir, Ritonavir, Saquinavir, Telaprevir, Telithromycin, Voriconazoleb, Aprepitant, Conivaptan, Crizotinib, Diltiazem, Dronedarone, Erythromycin, Fluconazole, Imatinib, Isavuconazole, Nefazodone, Netupitant, Nilotinib, Posaconazolee, Tofisopam, Verapamil, Delavirdine
• Severe and moderate P450 CY3A4 inducers: Carbamazepine, Enzalutamide, Fosphenytoin, Mitotane, Phenytoin, Rifampicin, Bosentan, Efavirenz, St John's wort, Barbiturates, Nevirapine, Primidone, Rifabutin, Rifapentine
• Oral contraceptives

Exclusion criteria

for HV

• Contraindications to MRI scanning or exposure to gadolinium-based contrast agents
• Pregnancy in WOCBP
• eGFR<60 ml/min per 1.73 m2
• Severe respiratory disease with chronic hypoxia (sats <92%), known CO2 retention or need for home oxygen therapy