HAI Book 2025 - Flipbook - Page 249
Patsyuk, Yuliya
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Lower microstructural integrity of the locus coeruleus to entorhinal
cortex pathway is related to elevated astrocyte reactivity and tau burden in
cognitively unimpaired individuals: a 7T dMRI study
Yuliya Patsyuk1, Maxime Van Egroo1,2, Elise Beckers1,3, Nicholas J. Ashton4,5,6,7, Shorena
Janelidze8, Kaj Blennow4,9, Oskar Hansson8,10, Henrik Zetterberg4,9,11,12,13, Benedikt A. Poser14,15,
Heidi I.L. Jacobs1,2
1
Faculty of Health, Medicine and Life Sciences, Mental Health and Neuroscience Research Institute, Alzheimer Centre
Limburg, Maastricht University, Maastricht, NL
2
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and
Harvard Medical School, Boston, MA, US
3
GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, BE
4
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy
at the University of Gothenburg, Mölndal, SE
5
Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, NO
6
King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Maurice Wohl Institute Clinical
Neuroscience Institute, London, GB
7
NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London
and Maudsley NHS Foundation, London, GB
8
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, SE
9
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, SE
10
Memory Clinic, Skåne University Hospital, Malmö, SE
11
Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, GB
12
UK Dementia Research Institute at UCL, London, GB
13
Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, CN
14
Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht,
NL
15
Maastricht Brain Imaging Centre, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, NL
Introduction: Pre-tangle tau inclusions from the locus coeruleus (LC) are hypothesized to propagate to the initial
cortical site of tau pathology 3the entorhinal cortex (EC)3 via neuron-to-neuron transmission along its projections.
Examining the LC-EC pathway integrity in vivo might shed light on the mechanisms underlying the earliest
processes contributing to disease progression. Here, we investigated the relationship between microstructural
integrity of the LC-EC pathway and plasma AD-related biomarkers in cognitively normal adults along the adult
lifespan.
Methods: Forty-seven cognitively unimpaired participants (mean age=60.4±15.1y.; 23 females) (Table 1) underwent
a 7T MRI session including LC imaging and a multi-shell high-angular resolution diffusion imaging protocol. The
LC-EC pathway was reconstructed using probabilistic tractography. Microstructural integrity of the LC-EC
pathway was assessed with Fractional Anisotropy (FA), Mean Diffusivity (MD), and NODDI-derived metrics of
Neurite Density Index (NDI) and Orientation Dispersion Index (ODI). A control tract originating from the LC and
reaching prefrontal/frontal areas was also included. Additionally, blood samples were processed for plasma ADrelated biomarkers, including A´42/40 ratio, GFAP, NfL, pTau181, pTau217 and pTau231.
Results: Multiple robust linear regressions adjusted for age, sex and volume showed that lower FA in the LC-EC
tract associated with elevated levels of GFAP (p=.03) and pTau217 (p=.043). Conversely, MD was positively
associated with GFAP (p
