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

Paul A. YushkevichiD, Mónica MuñoziD, Maria Mercedes Iniguez de Onzono Martin, Ranjit Ittyerah, Sydney LimiD, Sadhana RavikumariD, Madigan L. BedardiD, Stephen PickupiD, Weixia LiuiD, Jiancong WangiD, Alex Ling Yu HungiD, Jade Lasserve, Nicolas Vergnet, Long XieiD, Mengjin Dong, Salena Cui, Lauren McCollum, John L. RobinsoniD, Theresa Schuck, Robin de FlorèsiD, Murray GrossmaniD, Matthew Dylan TisdalliD, Karthik Prabhakaran, Gabor Mizsei, Sandhitsu R. DasiD, , Ricardo InsaustiiD

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Abstract

Tau protein neurofibrillary tangles (NFT) are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimers disease (AD) and related dementias. Our knowledge of the pattern of NFT progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in AD, is based on conventional 2D 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 (MTL) specimens were used to construct 3D quantitative maps of NFT burden in the MTL at individual and group levels. These maps reveal significant variation in NFT burden along the anterior-posterior axis. While early NFT pathology is thought to be confined to the transentorhinal region, we find similar levels of NFT burden in this region and other MTL subregions, including amygdala, temporopolar cortex, and subiculum/CA1.

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