Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol

Introduction Loss of blood-brain barrier (BBB) integrity is
hypothesised to be one of the earliest microvascular signs
of Alzheimer’s disease (AD). Existing BBB integrity imaging
methods involve contrast agents or ionising radiation, and
pose limitations in terms of cost and logistics. Arterial
spin labelling (ASL) perfusion MRI has been recently
adapted to map the BBB permeability non-invasively. The
DEveloping BBB-ASL as a non-Invasive Early biomarker
(DEBBIE) consortium aims to develop this modified
ASL-MRI technique for patient-specific and robust BBB
permeability assessments. This article outlines the study
design of the DEBBIE cohorts focused on investigating
the potential of BBB-ASL as an early biomarker for AD
(DEBBIE-AD).
Methods and analysis DEBBIE-AD consists of a
multicohort study enrolling participants with subjective
cognitive decline, mild cognitive impairment and AD, as
well as age-matched healthy controls, from 13 cohorts.
The precision and accuracy of BBB-ASL will be evaluated
in healthy participants. The clinical value of BBB-ASL will
be evaluated by comparing results with both established
and novel AD biomarkers. The DEBBIE-AD study aims to
provide evidence of the ability of BBB-ASL to measure BBB
permeability and demonstrate its utility in AD and ADrelated pathologies.
Ethics and dissemination Ethics approval was obtained
for 10 cohorts, and is pending for 3 cohorts. The results of
the main trial and each of the secondary endpoints will be
submitted for publication in a peer-reviewed journal.