Abstract
AbstractAlthough Alzheimer’s disease (AD) is the most common form of dementia in the United States, development of therapeutics has proven difficult. Invertebrate alternatives to current mammalian AD models have been successfully employed to study the etiology of the molecular hallmarks of AD. The marine snail Aplysia californica offers a unique and underutilized system in which to study the physiological, behavioral, and molecular impacts of AD. Mapping of the Aplysia proteome to humans and cross-referencing with two databases of genes of interest in AD research identified 898 potential orthologs of interest in Aplysia. Included among these orthologs were alpha, beta and gamma secretases, amyloid-beta, and tau. Comparison of age-associated differential expression in Aplysia sensory neurons with that of late-onset AD in the frontal lobe identified 59 ortholog with concordant differential expression across data sets. The 21 concordantly upregulated genes suggested increased cellular stress and protein dyshomeostasis. The 47 concordantly downregulated genes included important components of diverse neuronal processes, including energy metabolism, mitochondrial homeostasis, synaptic signaling, Ca++ regulation, and cellular cargo transport. Compromised functions in these processes are known hallmarks of both human aging and AD, the ramifications of which are suggested to underpin cognitive declines in aging and neurodegenerative disease.
