title: Statin therapy for Alzheimer's disease: will it work?
abstract: Disease-modifying therapies are being developed for Alzheimer's disease (AD). These are expected to slow the clinical progression of the disease or delay its onset. Cerebral accumulation of amyloid beta (A beta) peptides is an early and perhaps necessary event for establishing AD pathology. Consequently therapies aimed at attenuating brain amyloidosis are expected to be disease modifying. Based on the epidemiological evidence pointing to a link between cholesterol metabolism and AD and the numerous laboratory studies implicating cholesterol in the process of A beta production and accumulation, it is now believed that cholesterol-lowering therapies will be of value as disease modifying agents. Several epidemiological studies revealed that statin use for the treatment of coronary arterial disease is associated with a decreased prevalence or a decreased risk of developing AD. These observations require both preclinical and clinical validation. The former involves testing statins in one or more animal models of AD in order to establish which disease features are affected by statin treatment, the relative efficacy with which different statins modify these features and the mechanism(s) by which statins affect AD phenotypes. The latter requires prospective, randomized, placebo controlled trials to evaluate the effect of statin treatment on cognitive and AD biomarker outcomes. We have initiated a study aimed at determining the effects of atorvastatin (Lipitor), a statin with the largest US market share, on brain A beta deposition in the PSAPP transgenic mouse model of Alzheimer's amyloidosis. Our results indicate that Lipitor treatment markedly attenuates A beta deposition in this animal model.
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Dementia Research Group, Orangeburg, NY, 10962, USA. petances@nki.rfmh.org
authors.forename: Suzana S
authors.initials: SS
authors.lastname: Petanceska
authors.forename: Steven
authors.initials: S
authors.lastname: DeRosa
authors.forename: Vicki
authors.initials: V
authors.lastname: Olm
authors.forename: Nichole
authors.initials: N
authors.lastname: Diaz
authors.forename: Ali
authors.initials: A
authors.lastname: Sharma
authors.forename: Tara
authors.initials: T
authors.lastname: Thomas-Bryant
authors.forename: Karen
authors.initials: K
authors.lastname: Duff
authors.forename: Miguel
authors.initials: M
authors.lastname: Pappolla
authors.forename: Lorenzo M
authors.initials: LM
authors.lastname: Refolo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D002784:Cholesterol; D000069059:Atorvastatin