Embodiments of the present invention are directed to various high-throughput methods for identifying compounds that are useful for the treatment of various neurodegenerative diseases, including the Huntington's Disease (HD), Parkinson's Disease (PD), Alzheimer's Disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Methods and compositions of the present invention enable the exogenous expression of one or more neurodegenerative-disease-related polypeptide variants within the ocular lens of an animal host. The formation of aggregates containing neurodegenerative-disease-related polypeptide variants increases the opacity of the lens, in a manner similar to the development of age-onset cataracts. The effect of a test compound in decreasing aggregate formation and/or destabilizing aggregates that contain neurodegenerative-disease-related polypeptide variants can be visually monitored and quantified in living animal hosts by employing conventional cataract-detecting instrumentation and related methods.