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

Patsyuk, Yuliya ; Van Egroo, Maxime ; Beckers, Elise ; Koops, Elouise A. ; Ashton, Nicholas J. ; Janelidze, Shorena LU ; Blennow, Kaj LU ; Hansson, Oskar LU orcid ; Zetterberg, Henrik LU and Poser, Benedikt A. , et al. (2025) In Alzheimer's and Dementia 21(12).
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... (More)

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.

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publication status
published
subject
keywords
Alzheimer's disease, biomarkers, diffusion tensor imaging, entorhinal cortex, locus coeruleus, magnetic resonance imaging, microstructural integrity, neurite orientation dispersion and density imaging, preclinical, tau, white matter
in
Alzheimer's and Dementia
volume
21
issue
12
article number
e70915
publisher
Wiley
external identifiers
  • scopus:105023334964
  • pmid:41319161
ISSN
1552-5260
DOI
10.1002/alz.70915
language
English
LU publication?
yes
id
8d112c0b-eed2-4e1e-a301-d10acdfd4df4
date added to LUP
2026-01-14 12:30:48
date last changed
2026-01-15 03:00:10
@article{8d112c0b-eed2-4e1e-a301-d10acdfd4df4,
  abstract     = {{<p>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.</p>}},
  author       = {{Patsyuk, Yuliya and Van Egroo, Maxime and Beckers, Elise and Koops, Elouise A. and Ashton, Nicholas J. and Janelidze, Shorena and Blennow, Kaj and Hansson, Oskar and Zetterberg, Henrik and Poser, Benedikt A. and Jacobs, Heidi I.L.}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; biomarkers; diffusion tensor imaging; entorhinal cortex; locus coeruleus; magnetic resonance imaging; microstructural integrity; neurite orientation dispersion and density imaging; preclinical; tau; white matter}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Locus coeruleus-entorhinal cortex tract integrity is linked to plasma tau and glial fibrillary acidic protein}},
  url          = {{http://dx.doi.org/10.1002/alz.70915}},
  doi          = {{10.1002/alz.70915}},
  volume       = {{21}},
  year         = {{2025}},
}