Studies have shown that protein insolubility increases with age. The proteins that become insoluble with age are enriched for lifespan determining functions. Knocking down some of the genes encoding the insoluble proteins has shown extension of lifespan in nematodes. Age-related Diseases, e.g. Alzheimer’s disease (AD) are known to be associated with protein aggregation, but it is not clear how normal aging processes and age-related disease processes are related. In this study, we investigated the insolublome (1% SDS insoluble proteins) of C. elegans in aging model (young vs. old for N2 and Ju775 strains) and disease model (human Ab expressing worms vs. control). We aim to decipher the significant changes and the possible correlation of insolublome in aging and age-related disease. Our preliminary results indicate normal aging as an important driver, and relevant observations to reveal the molecular mechanism of AD pathology.