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

• Published in: Brain (London, England : 1878) Vol. 144; no. 9; pp. 2784 - 2797
• Main Authors: 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, Wang, Jiancong, Hung, Ling Yu, Lasserve, Jade, Vergnet, Nicolas, Xie, Long, Dong, Mengjin, Cui, Salena, McCollum, Lauren, Robinson, John L, Schuck, Theresa, de Flores, Robin, Grossman, Murray, Tisdall, M Dylan, Prabhakaran, Karthik, Mizsei, Gabor, Das, Sandhitsu R, Artacho-Pérula, Emilio, Arroyo Jiménez, Marı'a Del Mar, Marcos Raba, Marı'a Pilar, Molina Romero, Francisco Javier, Cebada Sánchez, Sandra, Delgado González, José Carlos, de la Rosa-Prieto, Carlos, Córcoles Parada, Marta, Lee, Edward B, Trojanowski, John Q, Ohm, Daniel T, Wisse, Laura E M, Wolk, David A, Irwin, David J, Insausti, Ricardo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 22-10-2021
• Subjects: Aged; Aged, 80 and over; Alzheimer's disease; Basic Medicine; Brain Mapping - methods; Cohort Studies; Female; Humans; Imaging, Three-Dimensional - methods; Magnetic Resonance Imaging - methods; Male; medial temporal lobe; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Middle Aged; neurodegeneration; neurofibrillary tangles; Neurofibrillary Tangles - pathology; Neurosciences; Neurovetenskaper; Original; Temporal Lobe - diagnostic imaging; Temporal Lobe - pathology; neurodegeneration; medial temporal lobe; Alzheimer’s disease; neurofibrillary tangles
• ISSN: 0006-8950; 1460-2156
• DOI: 10.1093/brain/awab262

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.