The coupling of global brain activity and cerebrospinal fluid flow as a potential predictive marker of amyloid-β accumulation

Motivation: Early identification of individuals at risk for amyloid-β (Aβ) accumulation could enable upstream therapeutic interventions that target clearance dysfunction. Goal(s): To investigate whether global Blood-Oxygen-Level-Dependent signals (gBOLD) - cerebrospinal fluid (CSF) coupling, a novel indicator of brain clearance function, can identify a future Aβ-positive group in cognitively normal elderly individuals. Approach: Amyloid converters showed significantly weaker coupling, indicating reduced brain clearance function, with a correlation observed between coupling strength and Aβ accumulation rate. Results: Amyloid converters showed significantly weaker coupling, indicating reduced brain clearance function, with a correlation observed between coupling strength and Aβ accumulation rate. Impact: This study clarifies that reduced CSF clearance causes brain Aβ accumulation and demonstrates that gBOLD-CSF coupling could serve as a non-invasive biomarker for predicting future brain Aβ accumulation, potentially enabling pre-preclinical Alzheimer's disease interventions that target clearance dysfunction.