Alzheimer disease: 100 years later

Citation
L. Puglielli et Dm. Kovacs, Alzheimer disease: 100 years later, REV MED CHI, 129(5), 2001, pp. 569-575
Citations number
43
Categorie Soggetti
General & Internal Medicine
Journal title
REVISTA MEDICA DE CHILE
ISSN journal
00349887 → ACNP
Volume
129
Issue
5
Year of publication
2001
Pages
569 - 575
Database
ISI
SICI code
0034-9887(200105)129:5<569:AD1YL>2.0.ZU;2-G
Abstract
Almost 100 years since the first clinical report of a case of Alzheimer dis ease (AD), three early-onset and two late-onset AD genes have been identifi ed. While rare mutations in the early-onset genes (amyloid precursor protei n, and presenilins 1 and 2) lead to increased generation of specific forms of the amyloid beta protein (A,beta), common polymorphisms in the late-onse t 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 neurodege neration has not yet been attained, mechanism-based approaches for the ther apeutic treatment of AD based on lowering levels of the potentially pathoge nic A beta are currently underway. The recent discovery of the enzymes (sec retases) responsible for generating A beta have paved the way for the devel opment of such drugs and increase the prospects for successful therapeutic intervention to arrest AD neuropathogenesis (Rev Med Chile 2001; 129: 569-7 5).