Abstract
Alzheimers Dement. 2025 Dec;21(12):e70915. doi: 10.1002/alz.70915.
ABSTRACT
INTRODUCTION: Pretangle tau inclusions from the locus coeruleus (LC) are hypothesized to propagate to the entorhinal cortex (EC) via neuron-to-neuron transmission along its projections. The lower integrity of the LC-EC pathway accompanying Alzheimer's disease (AD) pathology is supported by post mortem studies, but in vivo evidence remains limited.
METHODS: We associated diffusion-weighted 7T magnetic resonance imaging (MRI) metrics of microstructural integrity within the LC-EC tract to plasma AD-related biomarkers in a cohort of 47 cognitively unimpaired adults.
RESULTS: Worse overall and local LC-EC integrity, indicated by lower fractional anisotropy (FA) and higher mean diffusivity (MD), was related to elevated concentrations of plasma phosphorylated tau 181 (p-tau181), p-tau217, and glial fibrillary acidic protein (GFAP). A higher orientation dispersion index (ODI) within the LC-EC tract was linked to elevated plasma p-tau181 and p-tau231 levels.
DISCUSSION: The lower integrity of the LC-EC pathway may serve as a key indicator of the earliest AD-related pathophysiological processes to improve detection of at-risk individuals.
HIGHLIGHTS: Standard DTI model metrics in the LC- EC tract are linked to elevated plasma p-tau and GFAP. A higher ODI in the voxels containing the LC-EC tract is related to elevated plasma p-tau. LC-EC integrity links to AD-related biomarkers show topographic specificity. Lower LC-EC integrity may be a key indicator of the earliest AD-related pathology.
PMID:41319161 | DOI:10.1002/alz.70915
UK DRI Authors
