title: In vitro effect of PPAR-gamma2 Pro12Ala polymorphism on the deposition of Alzheimer's amyloid-beta peptides.
abstract: Mounting evidence suggests that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is involved in the modulation of pathogenic events related to Alzheimer's disease (AD). Such events would include the cerebral deposition of amyloid-beta (Abeta) and the consequent local inflammatory response. PPAR-gamma has been shown to act on both fronts, reducing either the secretion of Abeta or the expression of pro-inflammatory cytokines. Recently, the relatively common Pro12Ala polymorphism in exon 2 of PPAR-gamma has been associated with higher risk for late onset AD. Here, we compare the effect of PPAR-gamma and its genetic variant on the secretion of Abeta. Our results indicate that, in neuronal cultured cells, the Pro12Ala substitution does not affect the anti-amyloidogenic capacity of PPAR-gamma. Additional factors, PPAR-gamma related, may therefore predispose aged subjects, carrying the Ala allele, to develop the neurodegenerative disease.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: d'Abramo
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Zingg
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Francesca
authors.initials: F
authors.lastname: Argellati
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
mesh_terms: D000409:Alanine / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002461:Cell Line, Transformed; D003001:Cloning, Molecular / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000502:physiology*; D011392:Proline / Q000235:genetics; D014162:Transfection / Q000379:methods