title: Lysosomal generation of amyloid beta protein species in transgenic mice.
abstract: Soluble amyloid beta protein (A beta)1-40 and highly amyloidogenic A beta 1-42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the A beta precursor. A beta 1-42/43 and long A beta species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with A beta fibrils. These findings indicated that A beta 1-40, A beta 1-42, A beta 1-43 and longer A beta species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate gamma-secretase, leads to acceleration of A beta amyloid formation.
authors.affiliation: Department of Neurology, Gunma University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawarabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Igeta
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Sasaki
authors.forename: E
authors.initials: E
authors.lastname: Matsubara
authors.forename: M
authors.initials: M
authors.lastname: Kanai
authors.forename: Y
authors.initials: Y
authors.lastname: Tomidokoro
authors.forename: K
authors.initials: K
authors.lastname: Ishiguro
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.forename: S
authors.initials: S
authors.lastname: Hirai
authors.forename: M
authors.initials: M
authors.lastname: Shoji
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor