Journal Article

Locus coeruleus‐entorhinal cortex tract integrity is linked to plasma tau and glial fibrillary acidic protein

Janelidze, Shorena, Jacobs, Heidi I. L., Poser, Benedikt A., Blennow, Kaj, Zetterberg, Henrik, Beckers, Elise, Patsyuk, Yuliya, Ashton, Nicholas J., Van Egroo, Maxime, Koops, Elouise A., Hansson, Oskar

2025

Overview

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.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adults / Aged / Alzheimer Disease - blood / Alzheimer Disease - pathology / Alzheimer's disease / Basic Medicine / Biological markers / Biomarkers / Biomarkers - blood / Cellular and Molecular Neuroscience / Cortex / Developmental Neuroscience / Diffusion Magnetic Resonance Imaging / diffusion tensor imaging / Entorhinal cortex / Entorhinal Cortex - diagnostic imaging / Entorhinal Cortex - pathology / Epidemiology / Female / Geriatrics and Gerontology / Glial Fibrillary Acidic Protein / Glial Fibrillary Acidic Protein - blood / Health Policy / Human health sciences / Humans / locus coeruleus / Locus Coeruleus - diagnostic imaging / Locus Coeruleus - pathology / Magnetic resonance imaging / Male / MAPT protein, human / Medical and Health Sciences / Medicin och hälsovetenskap / Medicinska och farmaceutiska grundvetenskaper / microstructural integrity / Middle Aged / Morality / Neural Pathways / Neural Pathways - diagnostic imaging / Neural Pathways - pathology / neurite orientation dispersion and density imaging / Neurologie / Neurology / Neurology (clinical) / Neurosciences / Neurosciences & behavior / Neurosciences & comportement / Neurovetenskaper / Pathology / preclinical / Projections / Psychiatry and Mental Health / Radiologie, médecine & imagerie nucléaire / Radiology, nuclear medicine & imaging / Sciences de la santé humaine / Sciences sociales & comportementales, psychologie / Social & behavioral sciences, psychology / Software / tau / tau Proteins / tau Proteins - blood / white matter