Fig. 3

Endotoxin may give rise to different neurodegenerative disease by synergising with different aggregable proteins to induce neurodegeneration. If endotoxin contributes to multiple different diseases, why are these different diseases different? The solution may be a two-hit hypothesis, where the presence of endotoxin or an aggregable protein is not sufficient alone, but together, they induce neurodegeneration and give rise to different neurodegenerative diseases dependent on the particular aggregable protein present and its distribution in the brain. Note that the presence in the brain of an aggregable protein, such as Aβ, Tau or α-synuclein, is not normally sufficient to induce neurodegeneration