Thalamic nucleus reuniens – hippocampal CA1 pathways as a possible Alzheimer biomarker.
Poster No:
37
Submission Type:
Late-Breaking Abstract Submission
Authors:
Merel Jager1, Dylan Taylor2, Hayat Kheir2, Lenore Tahara-Eckl2, Julie Vidal3, Nicola Slater4, Meg Spriggs2, Meghan van der Meer2, Cameron Heyman2, Tracy Melzer3, Reece Roberts2, Catherine Morgan2, Nick Cutfield5, Tim Anderson4, Campbell Le Heron4, Lynette Tippett2, John Dalrymple-Alford6, Ian Kirk2
Institutions:
1University of Groningen, Groningen, Groningen, 2University of Auckland, Auckland, New Zealand, 3University of Canterbury, Christchurch, New Zealand, 4University of Otago, Christchurch, New Zealand, 5University of Otago, Dunedin, New Zealand, 6University of Canterbury / New Zealand Brain Research Institute, Christchurch, New Zealand
First Author:
Co-Author(s):
John Dalrymple-Alford
University of Canterbury / New Zealand Brain Research Institute
Christchurch, New Zealand
University of Canterbury / New Zealand Brain Research Institute
Christchurch, New Zealand
Introduction:
The nucleus reuniens (Re) is a midline thalamic nucleus that is reciprocally connected to the medial prefrontal cortex and the CA1 region of the hippocampus (Vertes, et al., 2007). Over thirty years ago, Braak & Braak (1991) noted the occurrence of neurofibrillary tangles in the Re of Alzheimer's patients post-mortem in the absence of amyloid plaques. Last year, Censi, et al. (2024) suggested that Re atrophy, relative to atrophy in other thalamic structures, is the most significant predictor for the conversion of amnestic mild cognitive impairment (aMCI) to AD. In humans, the Re is a relatively small region, but Reeders et al., (2023) showed that the region can be readily identified in vivo using probabilistic tractography. As it is likely that white matter demyelination and degeneration appears earlier than abnormal changes in grey matter (Lee, et al., 2015), we hypothesized that white matter abnormalities in the tract between the nucleus reuniens and the CA1 region of the hippocampus might be an early marker of Alzheimer's disease.
Methods:
Diffusion Magnetic Resonance Imaging (dMRI) enables the investigation of these white matter structures. This study serves as a proof of concept to determine whether it is possible to identify, isolate, and compare the tracts connecting the Re and the CA1 region of the HC. DMRI data (n = 9) was used to generate plausible streamlines via anatomically constrained tractography in Mrtrix3 (Tournier, et al., 2019). Probabilistic atlases segmented the thalamus and hippocampus to define the Re and CA1, respectively, allowing for the extraction of streamlines between these regions.
Results:
Two distinct tracts were identified: one running anteriorly and another posteriorly (Figure 1). Sufficient streamlines were recovered to allow for diffusion metric extraction, confirming that this method can be used to quantify microstructural properties of these pathways. Here we extracted metrics using two models: diffusion tensor models (Basser, et al. 1994; Jones, 2014; Tournier, et al., 2019); and a Neurite Orientation Dispersion and Density Imaging model (NODDI; Zhang, et al., 2012). Two metrics were extracted from diffusion tensor models: the apparent diffusion coefficient (ADC), reflecting overall mobility of water molecules, with higher values indicating more diffusion; and fractional anisotropy (FA), reflecting the degree of directional preference of water diffusion in tissue, with higher values indicating greater integrity of white matter fiber tracts (Pierpaoli, et al., 1996). Two further metrics were derived from the NODDI model: the intracellular volume fraction (FICVF), reflecting the proportion of tissue water within the intracellular compartment relative to the overall water signal in a voxel, with higher values suggesting higher neurite density; and the orientation dispersion index (ODI), quantifying the degree of angular variability of neurites, with higher values indicating a more dispersed microstructure (Zhang, et al., 2012). Figure 2 demonstrates that these diffusion-based metrics can be extracted, standardized and compared between groups along the tracts of interest.
Conclusions:
These extracted metrics provide complementary insights into white matter microstructure and integrity, potentially helping to detect early neurodegenerative changes. At this stage (i.e. a small n), it is too early to conclude that significant differences exist between groups. However, this study establishes that the Re-CA1 connections can be reliably mapped, providing a foundation for future investigations. More subjects or longitudinal data is necessary to determine whether Re-HC tract metrics can serve as biomarkers for Alzheimer's disease.
Brain Stimulation:
Non-invasive Magnetic/TMS 1
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Keywords:
Aging
Degenerative Disease
MRI
STRUCTURAL MRI
Sub-Cortical
Systems
Thalamus
Tractography
White Matter
1|2Indicates the priority used for review
Abstract Information
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2. Braak, H., & Braak, E. (1991). Alzheimer's disease affects limbic nuclei of the thalamus. Acta Neuropathologica, 81(3), 261–268.
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