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Invertebrate alternatives to current mammalian AD models have been successfully employed to study the etiology of the molecular hallmarks of AD. The marine snail<jats:italic>Aplysia californica<\/jats:italic>offers a unique and underutilized system in which to study the physiological, behavioral, and molecular impacts of AD. Mapping of the<jats:italic>Aplysia<\/jats:italic>proteome to humans and cross-referencing with two databases of genes of interest in AD research identified 898 potential orthologs of interest in<jats:italic>Aplysia<\/jats:italic>. Included among these orthologs were alpha, beta and gamma secretases, amyloid-beta, and tau. Comparison of age-associated differential expression in<jats:italic>Aplysia<\/jats:italic>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<jats:sup>++<\/jats:sup>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.<\/jats:p>","DOI":"10.1007\/s12031-021-01918-3","type":"journal-article","created":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T06:15:32Z","timestamp":1634624132000},"page":"287-302","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Aplysia Neurons as a Model of Alzheimer\u2019s Disease: Shared Genes and Differential Expression"],"prefix":"10.1007","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-003X","authenticated-orcid":false,"given":"Nicholas S.","family":"Kron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne A.","family":"Fieber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"key":"1918_CR1","doi-asserted-by":"crossref","unstructured":"Abdel-Nour M et al (2019)\u00a0The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling. 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