Testing the amyloid toxicity hypothesis of Alzheimer's disease in transgenic Caenorhabditis elegans model

A Gutierrez-Zepeda
Y Luo

Abstract

Alzheimer's disease ( AD) is affecting more people every year due to the increase in elderly population. This disease is characterized by senior plaques, containing aggregated amyloid beta peptide ( A beta), and neurofibrillary tangles in the AD brains. The A beta depositions are thought to increase in cellular oxidative stress, which subsequently produces neuronal cell death in the patient's brain, causing loss of memory and, in the latter stages, dementia. Diverse models have been established to test this "Amyloid Toxicity Hypothesis of AD". Among these, the use of the nematode Caenorhabditis elegans has some advantages. This invertebrate has its entire genome known, as well as numerous gene homologues to those seen in humans. In relationship with the cell model, the nematode gives the benefit of an organismal view of the disease. The nematode's short life span proves useful, when compared with that of mice, allowing mechanistic studies of the disease and pharmacological treatments. Alongside with other laboratories, we have used this in vivo model to correlate the A expression with its toxicity through the observance of the organism's behavior to provide a better understanding of the cellular processes underlining AD.