Fig. 8.
Tau pathological burden is related to α-synuclein pathology in LRRK2 mutation carriers. Many regions of the brain had multiple pathologies co-occurring. To understand whether there is an association of the different pathologies with each other, each pathology was plotted against the other by region (a-e). While Aβ burden showed no relationship to tau or α-synuclein burden (a Aβ x AT8: R2adj = − 0.01, p = 0.6054; b Aβ x GT-38: R2adj = − 0.01, p = 0.7676; c Aβ x pSyn: R2adj = 0.01, p = 0.2091), pSyn pathology was positively associated with tau pathology (d pSyn x AT8: R2adj = 0.11, p = 0.001261; e pSyn x GT-38: R2adj = 0.10, p = 0.002507), suggesting that the two pathologies may influence each other or may both be influenced by a common factor. To further parse out whether tau pathology was a separate neuropathological substrate of disease in cases without α-synuclein pathology, cases were separated by pSyn pathology (f-i). Of the 12 LRRK2 mutation carriers, 5 of them clearly had no pSyn pathology present in any of the areas examined. AT8 (f), GT-38 (g) and pSyn (h) pathology was on average elevated in the brains of individuals with pSyn pathology, although only the pSyn levels were statistically different. In contrast, Aβ load was not different between the two groups (i). (f-h) Mann-Whitney tests: AT8: p = 0.3434; GT-38: p = 0.5303; pSyn: p = 0.0025. (i) Unpaired t-test: Aβ: p = 0.8598