Figure 6.

Knockdown of AD‐enriched aggregate proteins rescues aggregation‐induced traits. (A) Proteins shown are overrepresented (in LC‐MS spectral counts) in aggregates isolated from AD relative to NC, except microtubule‐associated protein tau, which is hyperphosphorylated but not more abundant in AD (Table 1). Blue arrows connecting diamond symbols show increased abundance of proteins in tau‐IP aggregates; black arrows connecting triangles show increased abundance in Aβ‐IP aggregates. (B) Of 21 protein types more abundant in AD than in NC aggregates, knockdown of 14 (67%) of their nematode orthologs significantly rescued paralysis of a C. elegans strain expressing human Aβ1‐42 in muscle (blue bars), or rescued chemotaxis disrupted by neuronal expression of Aβ1‐42 (red bars). Significance was assessed by 1‐tailed t‐tests (as lower cytotoxicity was predicted) comparing fractions of unparalyzed or chemo‐attracted worms in three independent assays per group (*P < 0.05; **P < 0.005; ***P < 0.0005). Significance by chi‐squared tests within assays was P < 5 × 10−5 to 10−16.