Decreased water exchange rate across the blood-brain barrier throughout the Alzheimer's disease continuum: Evidence from Chinese data.

INTRODUCTION

Water exchange rate (Kw) across the blood-brain barrier (BBB) is used in magnetic resonance imaging (MRI) techniques to evaluate BBB functionality. Variations in BBB Kw across the Alzheimer's disease (AD) continuum remain uncertain.

METHODS

The study encompassed 38 cognitively normal individuals without AD biomarkers (CN_A-), 30 cognitively normal (CN_A+), and 31 cognitively impaired individuals (CI_A+) with positive AD biomarkers. Participants underwent clinical assessments, MRI/positron emission tomography scans, and assays of plasma biomarkers.

RESULTS

Significantly lower Kw was observed in multiple brain regions throughout the AD continuum. This alteration in Kw correlated with plasma biomarkers and neuropsychological performance. Elevated levels of phosphorylated tau 217 intensified the inverse relationship between Kw and neuropsychological performance. The integration of Kw, brain volume, and plasma biomarkers demonstrated potential in distinguishing stages within the AD continuum.

DISCUSSION

Consistently lower Kw was evident across the AD continuum and may act as a diagnostic tool for early AD screening.

HIGHLIGHTS

Observations revealed a decline in water exchange rate (Kw) across multiple brain regions within the Alzheimer's disease (AD) continuum, notably in the hippocampus, parahippocampal gyrus, and deep brain nuclei during the preclinical stage of AD. Strong correlations were established between Kw levels in various brain regions and plasma biomarkers, as well as neuropsychological performance in the AD continuum. Interaction between plasma phosphorylated tau (p-tau)217 and Kw in the hippocampus was linked to executive function, indicating a combined detrimental impact on cognitive abilities stemming from both blood-brain barrier Kw and p-tau 217. The combined use of Kw, brain volume, and plasma biomarkers-neurofilament light chain and glial fibrillary acidic protein-demonstrated potential for distinguishing individuals within the AD continuum.