Alzheimer’s Disease (AD) is the most common form of dementia and cognitive dysfunction, currently affecting approximately 5.5 million people in the United States. AD is a neurodegenerative disease which is characterized pathologically by the aggregation of neurotoxic amyloid-β (Aβ) peptides, derived from the proteolytic cleavage of a myloid precursor protein(APP), into insoluble plaques. Variants in the gene coding for APP have been shown to impact individual predisposition to AD. Two such mutant variants are the Swedish mutation and the Icelandic mutation, which have been shown to increase the risk of AD and protect against AD, respectively. In this paper, we investigate current literature to compare these two mutant variants, as well as to understand their effects on APP processing and development of neurotoxicity. Additionally, we investigate the historical components leading to the discovery of these variants to better understand future directions in AD research. To further elucidate the protective mechanism underlying the Icelandic mutation, we studied the effects of transient transfection with either the Swedish or Icelandic mutant of the APP gene, independently and co-transfected with Aβ, on apoptosis in an HT22 hippocampal cell line. Our preliminary findings suggest that the Icelandic mutant of APP may modulate susceptibility to Aβ-induced neurotoxicity through mechanisms distinct from merely altering APP processing. Future work is necessary to define these mechanisms and unravel the mystery of the Icelandic mutant’s neuroprotective effects.