Fig. 4.

In healthy brains, supersaturated proteins are highly expressed in tissues and cells vulnerable to neurodegenerative processes. (A) Red regions in the brain on the left indicate an elevated expression of supersaturated proteins relative to the proteome, while blue regions indicate an average expression below that of the proteome as a whole. Red regions in the brain on the right indicate the tissues most vulnerable to neurodegenerative processes associated with the early stages of AD, PD, FTD and ALS (see panel B and Table S1). (B) Box plot of Δ scores of the top 5% of supersaturated proteins (red) compared to the whole proteome (grey) calculated for AD, PD, ALS and FTD (x-axis). For each disease, Δ scores represent expression in vulnerable tissues, relative to expression in resistant tissues (see Experimental Procedures). The Δ scores reported for PD, ALS and FTD are calculated with the same procedure described in Experimental Procedures for AD, using the disease-specific vulnerable regions defined in Table S1. *****p < 0.00001; the statistical significance of the differences between the distributions of supersaturated proteins and that of the proteome was calculated with a t-test. In addition, a one tailed t-test was used to test that the distribution of relative expression scores for supersaturated proteins is greater than zero. This test yielded a p value of less than 0.00001 for tissues vulnerable to AD, PD, ALS and FTD. The dashed line at Δ = 0 (NV) indicates non-vulnerable tissues.