Lysosomal generation of amyloid beta protein species in transgenic mice.
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.
Kawarabayashi
T
T
Department of Neurology, Gunma University School of Medicine, Japan.
Igeta
Y
Y
Sato
M
M
Sasaki
A
A
Matsubara
E
E
Kanai
M
M
Tomidokoro
Y
Y
Ishiguro
K
K
Okamoto
K
K
Hirai
S
S
Shoji
M
M
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
D016564:Amyloid beta-Protein Precursor