Ultra-high-performance Positron Emission Tomography (PET) of Synaptic Density, Reactive Astrogliosis and Tau in Alzheimer's Disease

AIM: to investigate the relationship between synaptic density, tau and reactive astrogliosis in Alzheimer's disease (AD) versus healthy controls and centenarians. DESIGN: this cross-sectional study will recruit patients with biomarker-proven AD, age- and sex-matched healthy controls as well as centenarians. All subjects will undergo a neuropsychological evaluation and ultra-high-performance PET imaging sessions with 18F-SynVesT-1 (synaptic density), 18F-MK6240 (tau) and 18F-SMBT-1 (reactive astrogliosis) as well as structural and diffusion MRI. Blood samples will be taken for the evaluation of blood-based biomarkers.

\- Patients with Alzheimer's disease (AD) Inclusion Criteria: * Patient has a clinical diagnosis of biomarker proven AD (prodromal AD or dementia due to AD). * Patient has an mini-mental state examination (MMSE) score of 15 or higher. * Patient or legal representative is able to understand the patient information brochure and give written informed consent. Exclusion Criteria: * Patient has a history of any major other disease that may interfere with the investigations or make the subject unfit for participation according to the interpretation by the investigator. * Patient is on anti-amyloid therapy. * Patient has contra indications for magnetic resonance imaging (MRI). * Patient is a current smoker. * Patient is currently a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse. Healthy control participants Inclusion Criteria: * Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures * Participant is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs, clinical laboratory test and urinalysis. * No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment (Geriatric depression scale (GDS) and Beck's depression inventory (BDI)). * A normal structural MRI scan with respect to the participant's age as assessed by expert radiologist. * Participant has to be at least 40 years old Exclusion Criteria: * Participant has a history of any major disease that may interfere with the investigations or make the subject unfit for participation according to the interpretation by the investigator (especially diabetes mellitus, heart disease, liver and kidney disease, or most forms of cancer). * Participant is a smoker or has a recent history of smoking. * Participant has a history or evidence of psychiatric disease. * Participant is currently a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse. * Participant has a contra-indication for MRI scanning. * Participant suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures. Subject cannot lie still for at least 30 minutes inside a scanner. * Participant does not understand the study procedures. * Participant is unwilling or unable to perform all of the study procedures or is considered unsuitable in any way by the principal investigator. * Participant is pregnant or is breastfeeding. Centenarians Inclusion Criteria: * Participant is included in the 100-plus study at Amsterdam UMC. * Participant or legal representative is able to understand the information brochure and give written informed consent. Exclusion Criteria: * Participant has a history of any major disease that may interfere with the investigations or make the subject unfit for participation according to the interpretation by the investigator (especially diabetes mellitus, heart disease, liver and kidney disease, or most forms of cancer). * Participant is a current smoker. * Participant is currently a user (including ''recreational use'') of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse. * Participant has contra indications for MRI or cannot lie still in the scanner for 30 minutes.