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Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe

Yushkevich, Paul A. ; Muñoz López, Mónica ; Iñiguez De Onzoño Martin, María Mercedes ; Ittyerah, Ranjit ; Lim, Sydney ; Ravikumar, Sadhana ; Bedard, Madigan L. ; Pickup, Stephen ; Liu, Weixia and Wang, Jiancong , et al. (2021) In Brain 144(9). p.2784-2797
Abstract

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual... (More)

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, medial temporal lobe, neurodegeneration, neurofibrillary tangles
in
Brain
volume
144
issue
9
pages
14 pages
publisher
Oxford University Press
external identifiers
  • pmid:34259858
  • scopus:85116346295
ISSN
0006-8950
DOI
10.1093/brain/awab262
language
English
LU publication?
yes
id
268b40ed-e218-4ede-9b5b-a62d9e8f2a20
date added to LUP
2022-02-08 11:55:18
date last changed
2024-04-18 05:15:34
@article{268b40ed-e218-4ede-9b5b-a62d9e8f2a20,
  abstract     = {{<p>Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.</p>}},
  author       = {{Yushkevich, Paul A. and Muñoz López, Mónica and Iñiguez De Onzoño Martin, María Mercedes and Ittyerah, Ranjit and Lim, Sydney and Ravikumar, Sadhana and Bedard, Madigan L. and Pickup, Stephen and Liu, Weixia and Wang, Jiancong and Hung, Ling Yu and Lasserve, Jade and Vergnet, Nicolas and Xie, Long and Dong, Mengjin and Cui, Salena and McCollum, Lauren and Robinson, John L. and Schuck, Theresa and De Flores, Robin and Grossman, Murray and Tisdall, M. Dylan and Prabhakaran, Karthik and Mizsei, Gabor and Das, Sandhitsu R. and Artacho-Pérula, Emilio and Del Mar Arroyo Jiménez, Marl'a and Marcos Raba, Marl'a Pilar and Molina Romero, Francisco Javier and Cebada Sánchez, Sandra and Delgado González, José Carlos and De La Rosa-Prieto, Carlos and Córcoles Parada, Marta and Lee, Edward B. and Trojanowski, John Q. and Ohm, Daniel T. and Wisse, Laura E.M. and Wolk, David A. and Irwin, David J. and Insausti, Ricardo}},
  issn         = {{0006-8950}},
  keywords     = {{Alzheimer's disease; medial temporal lobe; neurodegeneration; neurofibrillary tangles}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{9}},
  pages        = {{2784--2797}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe}},
  url          = {{http://dx.doi.org/10.1093/brain/awab262}},
  doi          = {{10.1093/brain/awab262}},
  volume       = {{144}},
  year         = {{2021}},
}