Category: Neuroimaging (Non-PD)
Objective: Investigate the impact of Alzheimer’s disease (AD) co-pathology on an in vivo structural measure of neurodegeneration in Lewy Body disorders (LBD: Parkinson’s Disease and dementia with Lewy bodies).
Background: AD co-pathology occurs in ~50% of LBD cases at autopsy and may influence clinical features. Moreover, on structural imaging there is considerable variability in degree of cortical atrophy in LBD and sources of that variability are unclear. Here, we used regional digital pathology and cerebrospinal fluid (CSF)-biomarker to test the hypothesis that tau neuropathology in LBD associates with MRI cortical atrophy.
Method: We studied 71 LBD patients who underwent structural MRI in life and CSF analysis and/or neuropathological examination. The cohort was divided into LBD+AD (N=18) and LBD-AD (N=53) using criteria of medium/high level coexisting AD histopathology or an autopsy-validated CSF cut-off (t-tau/Aβ1-42>0.3). We first investigated the patterns of atrophy in a voxel-wise analysis of MRI cortical thickness estimates. Then, in a subgroup of 21 LBD patients who had participated in brain donation, we directly tested the association between ante-mortem MRI and post-mortem burden of tau, Aβ and alpha-synuclein (SYN) as quantified by digital histology in a set of 5 cortical regions (angular gyrus, visual cortex, anterior cingulate cortex, superior temporal cortex and medial frontal cortex).
Results: We found more pronounced MRI gray matter thinning of temporal pole, parahippocampal gyrus and superior temporal gyrus (p<0.05 FWE corrected) in LBD+AD relative to LBD-AD. There were significant negative correlations between cortical thinning and tau aggregation on digital histology across the sampled regions, after accounting for possible confounding effects of age, sex, and time interval between MRI and death (β=-0.1,p<0.05). Cortical thickness was not significantly associated with Aβ or SYN burden (p>0.15).
Conclusion: MRI cortical thinning is more pronounced in temporal regions in LBD+AD than LBD-AD is directly correlated with post-mortem histopathologic burden of tau, suggesting tau pathology influences patterns of neurodegeneration in LBD.
To cite this abstract in AMA style:
N. Spotorno, D. Coughlin, L. Shaw, A. Chen-Plotkin, D. Weintraub, E. Lee, J. Trojanowski, C. McMillan, D. Irwin, M. Grossman. Tau Neuropathology Associates with In Vivo Patterns of Neurodegeneration in Lewy Body Disorders [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/tau-neuropathology-associates-with-in-vivo-patterns-of-neurodegeneration-in-lewy-body-disorders/. Accessed June 12, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/tau-neuropathology-associates-with-in-vivo-patterns-of-neurodegeneration-in-lewy-body-disorders/