Amyloid-β Clearance Mechanisms in Alzheimer's Disease

Amyloid-β Clearance Mechanisms: A Multi-modal Study on Lymphatic, Glymphatic and Blood-brain-barrier Function in Alzheimer's Disease

The focus of this study is to examine the protein-plaque clearance (Aß) in relation to the blood-brain-barrier, the glymphatic system, brain lymphatic system and enzymatic degradation. In order to achieve this aim the investigators intend to study participants with a Subjective Cognitive Decline, Mild Cognitive Impairment and a mild Alzheimer's disease.

In this study, the investigators want to examine the different mechanisms of the accumulation and the clearance of Aß- deposits with imaging methods. One focus of the study is an improved characterisation of a blood-brain-barrier disorder (which seems to have an impact on the Aß-accumulation). Another main aim is to provide an improved mechanistic clearance model, which integrates crucial components such as the recently proposed cerebral glymphatic and lymphatic pathways, and which addresses the interaction between the different components and their individual contribution to Aβ removal from the brain. A possible connection between sleep and an altered transport mechanism will be analysed. The prospective study cohort (N ~60) will include patients with Mild Cognitive Impairment, mild clinical AD and Subjective Cognitive Decline. All study participants will undergo a detailed clinical and neuropsychological assessment according to a standardised protocol (i.a. MRI, PET, CSF, actigraphy). Follow-up assessments will not be performed in the present project, but are planned in a subsequent study, pending further funding.

Inclusion Criteria:

• Diagnosis of amnestic MCI or AD dementia or clinical normal
• Able to provide written informed consent
• Unchanged pharmacotherapy within 4 days prior to the study specific assessments
• Fluent in German

Exclusion Criteria:

• Unable to give informed consent or has a legal guardian
• Other severe mental disorder, e.g. schizophrenia or bipolar affective disorder
• Clinically relevant depression
• Acute suicidality
• Current alcohol, drug or medication abuse
• History of severe traumatic brain injury within 3 months prior to inclusion
• Structural lesions of the basal ganglia or brain stem
• Severe neurological disorder including (but not limited to) epilepsy, systemic disorders, stroke, repeated transient ischaemic attacks, increased brain intracranial pressure, normal pressure hydrocephalus
• Severe medical disorders including (but not limited to) heart failure, respiratory failure, uncontrolled severe arterial hypertension
• Electronic implants (e.g. cardiac pacemaker) or other MRI contraindication
• Renal failure > stage 3 (GFR < 30 mL/min)
• Pregnancy
• Unresolved malignancies within two years prior to inclusion
• Severe current infections or other chronic or systemic disorders
• Other circumstances which preclude participation based on the investigator's judgement