3D Mapping of TAU Neurofibrillary Tangle Pathology in the Human Medial Temporal Lobe

Yushkevich, Paul A.; Martı́n, Marı́a; Ittyerah, Ranjit; Lim, Sydney; Lavery, Madigan; Wang, Jiancong; Hung, Ling Yu; Vergnet, Nicolas; Ravikumar, Sadhana; Xie, Lin; Dong, Mengjin; deFlores, Robin; Cui, Salena; McCollum, Lauren; Ohm, Daniel T.; Robinson, John; Schuck, Theresa; Grossman, Murray; Tisdall, M. Dylan; Prabhakaran, Karthik; Mizsei, Gabor; Das, Sandhitsu R.; Artacho‐Pérula, Emilio; Jiménez, María del Mar Arroyo; López, Mayra; Rabal, María Pilar Marcos; Romero, Francisco Javier Molina; Lee, Edward B.; Trojanowski, John Q.; Wisse, Laura; Wolk, David A.; Irwin, David J.; Insausti, Ricardo

doi:10.1109/isbi45749.2020.9098462

Cited by 7 publications

(17 citation statements)

References 11 publications

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“…As previous studies have mostly analyzed gross MTL measures such as total hippocampal volume, the current study expands our knowledge by providing analyses of more granular MTL subregional measures. While TDP-43 pathology did not demonstrate associations with any specific MTL subregion, our dataset is growing and more quantitative measures for TDP-43 pathology are being generated [68] which in the future will allow for more fine-grained analyses or analyses in subgroups such as the recently introduced Limbic Agerelated TDP-43 Encephalopathy, or LATE [46].…”

Section: Discussionmentioning

confidence: 92%

“…In conclusion, this unique dataset revealed differential MTL subregional atrophy patterns with different neurodegenerative pathologies. While the current study is limited by the use of the semi-quantitative scores of the different pathologies in the contralateral hemisphere and thickness measurements at a small number of anatomical locations, we aim to improve on this in future work as we are collecting serial immunohistochemistry of these four pathologies in the same hemisphere as the MRI, and matching it to structural MRI, in a subset of the participants [54,68]. This will allow for the creation of 3D neurodegenerative pathology maps which can be directly linked to local neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

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Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

Wisse

Ravikumar

Ittyerah

et al. 2021

acta neuropathol commun

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The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-β and α-synuclein pathology were rated on a scale of 0 (absent)—3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman’s rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = − 0.27 to r = − 0.46), and (2) tau with BA35 (r = − 0.31) and SRLM thickness (r = − 0.33). In amyloid-β and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = − 0.40), BA35 (r = − 0.55), subiculum (r = − 0.42) and CA1 thickness (r = − 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-β suggests a role of Primary Age-Related Tauopathy in neurodegeneration.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

Wisse

Ravikumar

Ittyerah

et al. 2021

acta neuropathol commun

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“…Though both samples reflect end-stage pathology, the rostral-caudal gradient is consistent with the spread of tau outlined in Braak staging [5, 6], and supports recent work by Yushkevich et. al that found similar segregation of tau pathology in the anterior vs. posterior portions of hippocampal structures in cases of earlier stage disease [35].…”

Section: Discussionmentioning

confidence: 99%

“…Similar to other groups [35], we evaluated accuracy of alignment between 2D histology and 3D MRI by looking at sets of discrete points (pixels) labeled in 2D versus corresponding voxels labeled in 3D and subsequently deformed to 2D (see Figure 3). Here, our sets of points were the sets of pixels (voxels) within a particular MTL subregion as delineated on 2D histology images and 3D MRI (see Section 2.5).…”

Section: Competing Interestsmentioning

confidence: 99%

“…Several strategies for representing image similarity have emerged including cross-correlation [32], mutual information [33], and local textural characteristics [34]. Our approach is to extend previous work [35,36] by modelling a photometric transformation of histology to MRI with Mallat's Scattering Transform [37,38] to represent local radiomic textures at histological scales. Second, histological images carry large numbers of imperfections with tears, image stitching, and lighting variations.…”

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confidence: 99%

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Projective LDDMM: Spatially Reconstructing a Story of Rostrally-Dominant Tau in Alzheimer’s Disease

Stouffer

Chen

et al. 2022

Preprint

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Since Braak's initial histological observations, it has been recognized that Alzheimer's disease (AD) neurofibrillary tangles (NFTs) appear in the medial temporal lobe (MTL) of the brain very early in the disease course. MRI-based shape diffeomorphometry markers have demonstrated preclinical AD changes in the MTL but it has not been possible to confirm that these MRI changes correspond to the presence of NFTs. Here, we present a method termed Projective LDDMM for aligning sparse measurement profiles of AD pathology (i.e., 2D digital histology images) with 3D MRI. We reconstruct measures of 2D NFT density in the dense metric of 3D MRI, using the Mai Paxinos Atlas coordinates for two cases of advanced AD. Analyses reveal the highest levels of NFT density in the rostral third (10-15 mm) of the hippocampus and the adjoining regions of the entorhinal cortex and amygdala. These findings emphasize the selective vulnerability of MTL subregions in AD, and suggest that high resolution MRI methods might benefit from focusing on the rostral MTL to more closely link these MRI images to AD neuropathology.

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From Picoscale Pathology to Decascale Disease: Image Registration with a Scattering Transform and Varifolds for Manipulating Multiscale Data

Stouffer

Wang

et al. 2021

Multimodal Learning for Clinical Decision Support

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3D Mapping of TAU Neurofibrillary Tangle Pathology in the Human Medial Temporal Lobe

Cited by 7 publications

References 11 publications

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

Downstream effects of polypathology on neurodegeneration of medial temporal lobe subregions

Projective LDDMM: Spatially Reconstructing a Story of Rostrally-Dominant Tau in Alzheimer’s Disease

From Picoscale Pathology to Decascale Disease: Image Registration with a Scattering Transform and Varifolds for Manipulating Multiscale Data

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