title: Plasmin deficiency in Alzheimer's disease brains: causal or casual?
abstract: Substantial recent evidence suggests that defects in amyloid peptide degradation can be at the base of cases of sporadic Alzheimer's disease (AD). Among the discovered brain enzymes with the capacity to degrade amyloid peptide, the serine protease plasmin acquires special physiological relevance because of its low levels in areas of AD human brains with a high susceptibility to amyloid plaque accumulation. In this article we comment on a series of observations supporting the fact that plasmin paucity in the brain is not simply a secondary event in the disease but rather a primary defect in certain cases of sporadic AD. We also refer to recent data pointing to alterations in raft membrane domains and diminished membrane cholesterol as the underlying cause. Finally, we discuss the possibility that plasmin deficiency in the brain could lead to AD symptomatology because of amyloid aggregation and the triggering of cell death signaling cascades.
authors.affiliation: Cavalieri Ottolenghi Scientific Institute, Fondazione Cavalieri Ottolenghi, Università degli Studi di Torino, AO San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Dotti
authors.forename: Cristian
authors.initials: C
authors.lastname: Galvan
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Ledesma
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005341:Fibrinolysin / Q000172:deficiency*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism; D010958:Plasminogen / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010958:Plasminogen; D002784:Cholesterol; D005341:Fibrinolysin