Our working hypothesis
The availability of robust and sensitive imaging methodology for brain clearance is a prerequisite for understanding the development and progress of neurodegenerative diseases and the interaction with sleep. To allow its use as an early marker of early physiological effects linked to the development of neurodegenerative diseases, we see the need for at least two different markers:
Markers closely linked to transport of waste products involving tracers with a relevant molecular size to probe the exact same pathways as amyloid-beta would do. Such a marker can be both exploited to increase our knowledge on brain clearance as well as to measure brain clearance in high-risk subjects. Therefore, this marker can be minimally invasive, e.g. involve contrast agent administration either via intravenous or intrathecal injection.
Non-invasive markers that can be employed in larger cohort studies to assess early involvement of brain clearance impairment in neurodegenerative disease. Moreover, non-invasive markers have the advantage that they can easily be repeated in time (i.e. not depending on excretion of tracers from the body), making them especially attractive to monitor physiological changes in brain clearance during sleep.
