title: Familial Presenilin Mutations and Sporadic Alzheimer's Disease Pathology: Is the Assumption of Biochemical Equivalence Justified?
abstract: Studies of presenilin (PSEN) gene mutations producing early onset Alzheimer's disease (AD) have helped elucidate the pathogenic mechanisms of dementia and guided clinical trials of potential therapeutic interventions. Although familial and sporadic forms of AD share features, it is unclear if the two are precisely equivalent. In addition, PSEN mutations do not all produce a single phenotype, but exhibit substantial variability in clinical manifestations, which are related to the position and chemical nature of their amino acid substitutions as well as ratios of critical molecules such as Aβ40 and Aβ42. These differences complicate the interpretation of critical clinical trial results and their desired extrapolation to sporadic AD treatment. In this perspective, we examine differences between familial AD and sporadic AD as well as attributes shared by these uniquely arising disturbances in brain biochemical homeostasis that culminate in dementia.
authors.affiliation: Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
authors.affiliation: Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ, USA.
authors.forename: Chera L
authors.initials: CL
authors.lastname: Maarouf
authors.affiliation: Department of Microbiology, Midwestern University School of Medicine, Glendale, AZ, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kokjohn
mesh_terms: D000544:Alzheimer Disease / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation / Q000235:genetics*; D053763:Presenilins / Q000235:genetics* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053763:Presenilins
keywords: Amyloid-β; amyloid cascade hypothesis; dementia; familial Alzheimer’s disease; presenilin; sporadic Alzheimer’s disease