ABSTRACT
Mutations in the presenilin 1 (PS1) and presenilin 2 genes cosegregate with the majority of early-onset familial Alzheimer's disease (FAD) pedigrees. We now document that the Abeta1-42(43)/Abeta1-40 ratio in the conditioned media of independent N2a cell lines expressing three FAD-linked PS1 variants is uniformly elevated relative to cells expressing similar levels of wild-type PS1. Similarly, the Abeta1-42(43)/Abeta1-40 ratio is elevated in the brains of young transgenic animals coexpressing a chimeric amyloid precursor protein (APP) and an FAD-linked PS1 variant compared with brains of transgenic mice expressing APP alone or transgenic mice coexpressing wild-type human PS1 and APP. These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition.
Subject(s)
Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/genetics , Membrane Proteins/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Brain Chemistry/genetics , Culture Media, Conditioned , Gene Expression/physiology , Humans , Mice , Mice, Transgenic , Mutation/physiology , Neuroblastoma , Presenilin-1 , Recombinant Fusion Proteins/physiology , Transfection , Tumor Cells, Cultured/chemistry , Tumor Cells, Cultured/physiologyABSTRACT
Although Americans remain generally satisfied with the health care provided to them, sufficient access to high-quality, affordable health care for citizens without health care insurance has become an increasing problem in the last decade. Using the policy development process of the American Medical Association, Health Access America was conceived by the Association to improve access to affordable, high-quality health care. The proposal consists of six fundamental principles and 16 key points. This article specifically focuses on the five points that, if enacted into law, would improve access to health care for Americans who are, for various reasons, without health insurance.
