Fig. 3

The proportion of 3R tau-positive midbrain NFTs progressively increases with disease progression, while that of pontine NFT is persistently dominant over 4R tau. (a a-d, b a-d) The plots and best-fitted regression curves/lines of total counts of the NTs (a a-d) and NFTs (b a-d) against age at death, and Alzheimer-related cortical pathologies of the individual cases: i.e., cortical NFT stage, CERAD neuritic plaque score, and brain weight (descending order). Midbrain (navy triangle) and pons (orange oval). P-values of the Jonckheere’s one-sided test for the orderly increasing or decreasing trend are indicated at the right side of the regression models when p < 0.05. N.S.: not significant. The total counts significantly increased with advancing age and Alzheimer-related cortical pathologies, with minor exception (a d, the count of the midbrain NTs against brain weight reduction, Jonckheere’s trend test, p = 0.054). (a e, k, b e, k) Box plots of the arcsine-transformed proportion of 4R (green) and 3R (red) tau-positive lesions. Only pontine NFTs showed significantly higher overall mean of the proportion of 3R tau-positive lesions than that of the 4R tau (p = 0.0093 (*), paired t-test with Bonferroni correction). (a f-j, l-p, b f-j, l-p) Plots of arcsine-transformed proportion (4R tau/green rectangle, 3R tau/red triangle, 4R/3R tau both-positive/yellow oval) against age at death, cortical NFT stage, CERAD neuritic plaque score, brain weight (in inverse order), and the degree of local Aβ deposition at the midbrain and pons, with best-fitted regression models. P-values of Jonckheere’s trend test are noted when p < 0.05 (from top to bottom on the right side of each panel; 3R tau-positive/red, 4R tau-positive/green, 4R/3R tau both-positive/yellow). The proportion of 3R tau-positive and/or 4R/3R tau both-positive lesions showed significant increasing trends with advancing age and Alzheimer-related cortical pathologies, as well as local Aβ deposition, except for those of pontine NFTs, which remained stably elevated (b l-p)