Search

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.

Blood-brain-barrier (BBB) dysfunction is a hallmark of aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is time of exchange (Tex) of water across the BBB as measured by multi-echo arterial spin labeling MRI. We evaluated Tex across the age spectrum in 40 adults from two cohorts of healthy controls, and demonstrated that Tex is higher in gray than in white matter, higher in females than in males, and that Tex decreases with age. These findings suggest that BBB permeability changes over the lifespan can be investigated using arterial spin labeling approaches.

One of the earliest signs of Alzheimer’s disease (AD) is the loss of blood-brain barrier (BBB) integrity. Arterial spin labeling (ASL) MRI is a non-invasive way to measure perfusion and several other hemodynamic and physiological parameters, including vascular permeability. The DEveloping BBB-ASL as non-Invasive Early biomarker (DEBBIE) consortium aims to develop and integrate innovative techniques to allow robust BBB permeability assessments by ASL to develop a sensitive, non-invasive, and early biomarker for AD and related dementias. This work summarizes our planned efforts to develop and establish an MRI-based BBB permeability biomarker.

Blood-brain-barrier (BBB) dysfunction is a hallmark of aging-related disorders, including cerebral small vessel disease and Alzheimer’s disease. An emerging biomarker of BBB dysfunction is time of exchange (Tex) of water across the BBB as measured by multi-echo arterial spin labeling MRI. We evaluated Tex across the age spectrum in 40 adults from two cohorts of healthy controls, and demonstrated that Tex is higher in gray than in white matter, higher in females than in males, and that Tex decreases with age. These findings suggest that BBB permeability changes over the lifespan can be investigated using arterial spin labeling approaches.

Introduction: Loss of blood-brain barrier (BBB) integrity is hypothesized to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Arterial spin labeling (ASL) perfusion MRI has recently been adapted to map the BBB permeability non-invasively. This article outlines the study design of the DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium, focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD). Methods: DEBBIE-AD consists of 13 cohorts enrolling participants from subjective cognitive decline to AD, as well as healthy controls across the lifespan. The reproducibility and accuracy of BBB-ASL will be evaluated in healthy participants, and its clinical value will be evaluated with both established and novel AD biomarkers. Expected endpoints: DEBBIE-AD aims to provide evidence on the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD-related pathologies, which may provide new targets for treatment.

One of the earliest signs of Alzheimer’s disease (AD) is the loss of blood-brain barrier (BBB) integrity. Arterial spin labeling (ASL) MRI is a non-invasive way to measure perfusion and several other hemodynamic and physiological parameters, including vascular permeability. The DEveloping BBB-ASL as non-Invasive Early biomarker (DEBBIE) consortium aims to develop and integrate innovative techniques to allow robust BBB permeability assessments by ASL to develop a sensitive, non-invasive, and early biomarker for AD and related dementias. This work summarizes our planned efforts to develop and establish an MRI-based BBB permeability biomarker.