Abstract Details

Title Prediction of Regional Tau Spread Using Individualized Tau Epicenters and Structural Connectomes

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S39 - Neurobiology of Dementia (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Objective To predict the spread of tau in vivo based on structural connectivity with individualized epicenters of tau pathology.

Background Despite the fundamental association of tau pathology with functional impairment in Alzheimer’s disease, the factors that drive regional spread and the considerable individual differences in patterns of tau pathology remain poorly understood. Prior studies support spread of neurodegenerative pathology within brain networks and provide evidence of cell-to-cell transmission of pathologic proteins, which requires the transport of proteins along axons. Therefore, we hypothesized that spread of neuropathology requires a scaffolding of structural connectivity to propagate within the brain.

Design/Methods Tau PET (AV-1451) and DTI data from 29 participants across the clinical spectrum were included in the present study. T1-weighted and FLAIR images were used for FreeSurfer cortical segmentation. DTI and PET data were registered to T1-space using ANTs. Standardized uptake value ratios (SUVR) were calculated for each region using a cerebellar gray matter reference region. Multi-shell DTI data were collected in 113 non-collinear directions and 1.5mm isotropic voxels prior to pre-processing with a custom pipeline of tools to perform denoising, bias-correction, and eddy-current/motion correction with outlier replacement. BEDPOSTX and PROBTRACKX2 were used to perform probabilistic tractography between each FreeSurfer region. Network analysis was used to calculate the structural connectivity-based distance between all regions. The average connectivity-based distance from tau epicenters (regions with top 10% of tau SUVR in each hemisphere) was used in a linear-mixed model to predict regional SUVR.

Results A linear mixed-model demonstrated that regions with shorter connectivity-based distances from tau epicenters have higher tau burdens (F₁,_2362.5 = 298.39, p < 0.001, β = -0.022 [ -0.0246, -0.0197]). This model accounted for 40% of the total variance in tau SUVR.

Conclusions Individualized structural connectomes and epicenters of pathology predict regional tau burden and provide a tool for assessing expected propagation of pathology in vivo.

Authors/Disclosures
Christopher A. Brown, MD, PhD (Hospital of the University of Pennsylvania) PRESENTER	The institution of Dr. Brown has received research support from National Institute of Health.
	No disclosure on file
Ilya Nasrallah, MD, PhD	Dr. Nasrallah has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Nasrallah has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Nasrallah has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Nasrallah has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Cassiday Schade LLP. The institution of Dr. Nasrallah has received research support from NIH. The institution of Dr. Nasrallah has received research support from ASNR.
John A. Detre, MD (Hosp of the Univ of Penn)	Dr. Detre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hura Imaging. The institution of Dr. Detre has received research support from NIH. Dr. Detre has received personal compensation in the range of $500-$4,999 for serving as a grant proposal reviewer with NIH, VA, European Science Foundation,Deutsche Forschungsgemeinschaft.
	No disclosure on file
Corey McMillan, PhD (University of Pennsylvania)	Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. McMillan has received research support from Biogen. The institution of Dr. McMillan has received research support from NIH.
David A. Wolk, MD, FAAN (University of Pennsylvania)	Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.

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