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

被引：45

作者：

Yushkevich, Paul A. ^{[1
]}

Munoz Lopez, Monica ^{[2
]}

Iniguez de Onzono Martin, Maria Mercedes ^{[2
]}

Ittyerah, Ranjit ^{[1
]}

Lim, Sydney ^{[1
]}

Ravikumar, Sadhana ^{[1
]}

Bedard, Madigan L. ^{[1
]}

Pickup, Stephen ^{[1
]}

Liu, Weixia ^{[1
]}

Wang, Jiancong ^{[1
]}

Hung, Ling Yu ^{[1
]}

Lasserve, Jade ^{[1
]}

Vergnet, Nicolas ^{[1
]}

Xie, Long ^{[1
]}

Dong, Mengjin ^{[1
]}

Cui, Salena ^{[3
]}

McCollum, Lauren ^{[3
]}

Robinson, John L. ^{[4
]}

Schuck, Theresa ^{[4
]}

de Flores, Robin ^{[5
]}

Grossman, Murray ^{[3
]}

Tisdall, M. Dylan ^{[1
]}

Prabhakaran, Karthik ^{[3
]}

Mizsei, Gabor ^{[1
]}

Das, Sandhitsu R. ^{[3
]}

Artacho-Perula, Emilio ^{[2
]}

Arroyo Jimenez, Mari'a Del Mar ^{[2
]}

Marcos Raba, Mari'a Pilar ^{[2
]}

Molina Romero, Francisco Javier ^{[2
]}

Cebada Sanchez, Sandra ^{[2
]}

Delgado Gonzalez, Jose Carlos ^{[2
]}

De la Rosa-Prieto, Carlos ^{[2
]}

Corcoles Parada, Marta ^{[2
]}

Lee, Edward B. ^{[4
]}

Trojanowski, John Q. ^{[4
]}

Ohm, Daniel T. ^{[3
]}

Wisse, Laura E. M. ^{[6
]}

Wolk, David A. ^{[3
]}

Irwin, David J. ^{[3
]}

Insausti, Ricardo ^{[2
]}

机构：

[1] Univ Penn, Dept Radiol, 3700 Hamilton Walk,Suite D605, Philadelphia, PA 19104 USA

[2] Univ Castilla La Mancha, Neuromax CSIC Associated Unit, Human Neuroanat Lab, Albacete, Spain

[3] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

[4] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA

[5] INSERM, Caen, France

[6] Lund Univ, Dept Diagnost Radiol, Lund, Sweden

来源：

BRAIN | 2021年 / 144卷

基金：

美国国家卫生研究院;

关键词：

neurofibrillary tangles; Alzheimer's disease; neurodegeneration; medial temporal lobe; ALZHEIMERS-DISEASE; TAU PATHOLOGY; MEMORY; CORTEX; BRAIN; NEUROPATHOLOGY; REGISTRATION; PARCELLATION; ASSOCIATION; FAMILIARITY;

D O I：

10.1093/brain/awab262

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：2784 / 2797

页数：14

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