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. 2022 Jan 4;10:2. doi: 10.1186/s40478-021-01300-9

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 8 — Neurofibrillary degeneration. Graphs a-e illustrate regional differences in the percentage of neurons with NFTs and the progression of neurofibrillary degeneration from the incipient stage in pre-AD (26- to 41-year-old DS subjects) to three stages of AD in the fourth, fifth, and sixth decades. Fig. e shows the ratio between the percentage of neurons with NFTs in pre-AD and in AD and the gradient of susceptibility of neurons, with the highest in the entorhinal cortex, cornu Ammonis, subiculum, and amygdala; lower in the MBC, thalamus, and substantia nigra; and marginal in the caudate and dentate nuclei. The general pattern is illustrated in fig. f and g, showing a plateau of the percentage of neurons with NFTs in the fifth and sixth decades. Decrease of the number of neurons with NFTs from 10.3 million in the fifth decade to 8.5 million in the sixth decade is evidence of the death and removal of neurons with NFTs