title: Alzheimer disease: 100 years later.
abstract: Almost 100 years since the first clinical report of a case of Alzheimer disease (AD), three early-onset and two late-onset AD genes have been identified. While rare mutations in the early-onset genes (amyloid precursor protein, and presenilins 1 and 2) lead to increased generation of specific forms of the amyloid beta protein (A,beta), common polymorphisms in the late-onset genes (apolipoprotein E and alpha 2-macroglobulin) are thought to alter the clearance and degradation of A,beta in brain. Although definite proof for a direct link between altered A beta generation/clearance and neurodegeneration has not yet been attained, mechanism-based approaches for the therapeutic treatment of AD based on lowering levels of the potentially pathogenic A beta are currently underway. The recent discovery of the enzymes (secretases) responsible for generating A beta have paved the way for the development of such drugs and increase the prospects for successful therapeutic intervention to arrest AD neuropathogenesis.
authors.affiliation: Genetics and Aging Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Puglielli
authors.forename: D M
authors.initials: DM
authors.lastname: Kovacs
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D006801:Humans; D011110:Polymorphism, Genetic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor