Work

Coupling between global gray matter BOLD activity and CSF movement is associated with Aβ and tau burden in preclinical Alzheimer's disease

Year: 2025

Type: article

Abstract: BACKGROUND: Reduced glymphatic clearance may contribute to Alzheimer's disease. Low-frequency CSF flow, which mediates glymphatic clearance, has tight temporal coupling (i.e., anti-correlation) to global gray matter activity in resting-state BOLD-fMRI. But this coupling strength may decrease with AD. Evidence is needed on the association of gray matter BOLD (gBOLD)-CSF coupling with Aβ, tau, and neurodegeneration (ATN framework) in asymptomatic, preclinical AD. METHOD: generated using SRTM2 (reference=inferior cerebellum). RESULT: Mean age, 66.6 (SD=8.9); 57.1% women; 90.5% White; 52.4% APOE4 carriers. gBOLD-CSF coupling was negatively associated with tau in entorhinal (r=-0.49, p = 0.025), hippocampal (r=-0.55, p = 0.01), and amygdala ROIs (r=-0.58, p = 0.005). It showed weak negative association with global cortical Aβ (r=-0.40, p = 0.07) and parahippocampal and fusiform tau (r=-0.40, p = 0.07; r=-0.38, p = 0.085). gBOLD-CSF coupling was not associated with lingual tau and global synaptic density (ps>0.05). CONCLUSION: Contrary to our expectations, individuals with higher Aβ/tau showed stronger gBOLD-CSF anti-correlation. Reasons remain unclear, but it is possible that individuals with ATN were more likely to sleep during rsfMRI, leading to increased fluid movement. Our findings suggest the importance of adjusting for sleep-wake states when imaging brain fluid transport.

Source: Alzheimer s & Dementia

DOI: 10.1002/alz70855_106025