He amyloid forming Amyloid- domains may have been present in early deuterostomes, but more recent mutations appear to have resulted in potentially unrelated amyoid forming sequences. Our results further highlight that the species-specific physiological environment is as critical to Amyloid- formation as the peptide sequence. Keywords: Amyloid, Alzheimer disease, Phylogenetics, In silico, Aggregation, Maximum parsimony, Bayesian inferenceBackground The Amyloid- Precursor Protein (APP, APP) has been intensively studied due to its role in the generation of pathogenic cortical plaques in Alzheimer Disease [1]. It belongs to a gene family with deep evolutionary origins and is a member of a highly conserved protein family of type-1 transmembrane proteins [2-4]. The APP family consists of up to three homologues in vertebrate species: APP, amyloid precursor like protein 1 (APLP-1), and amyloid precursor like protein 2 (APLP-2). Invertebrate species genomes encode a single homologue referred to* Correspondence: [email protected] 1 Center for Clinical and Translational Science, University of Vermont, Given Courtyard N309, 89 Beaumont Avenue, Burlington, VT 05405, USA 3 Department of Microbiology and Molecular Genetics, University of Vermont, Given Courtyard N309, 89 Beaumont Avenue, Burlington, VT 05405, USA Full list of author information is available at the end of the articleas either amyloid precursor like 1 protein (APL-1) or APP-like 1 protein (APPL-1). Vertebrates and flatworms exhibit ubiquitous expression of at least one member of the APP family, while fruit flies express APPL-1 only in neurons. In all species, APP proteins are cleaved into multiple peptides and fragments by a series of proteases, but only vertebrate APP contains the sequence coding the pathological Amyloid- (A) peptide fragment. The -fold intrinsic to amyloid formation is a commonly observed biochemical property [5-7]. Amyloid formation is observed in non-pathological contexts from an efficient steric mechanism for storage of small peptide hormones to rudimentary forms of biological compartmentalization [5,8]. The neuropathological changes observed in the brains of patients with Alzheimer Disease led to the formation of the Amyloid2013 Tharp and Sarkar; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tharp and Sarkar BMC Genomics 2013, 14:290 http://www.biomedcentral/1471-2164/14/Page 2 ofHypothesis, which implicates both extracellular deposits of A fibrils and low-order intracellular A oligomers in the disruption of neuronal function, distortion of neural architecture, and induction of inflammation [1].Roxithromycin Mutations in the APP sequence and in associated proteases have been independently associated with familial early onset Alzheimer Disease characterized by rapidly progressive dementia and heavy A plaque burden [9].Fenofibrate Recently, a protective mutation in APP reducing the formation of A was identified [10].PMID:23415682 However, 95 of sporadic Alzheimer Disease exhibits no mutation in the APP gene sequence. Further, deposition of A is not limited to Alzheimer Disease. A plaques have been observed in vascular dementias, Lewy body dementia, and Parkinson Disease with dementia, as well as in the brains of aged individuals without any cognitiv.