Three-dimensional analysis of abnormal ultrastructural alteration in mitochondria of hippocampus of APP/PSEN1 transgenic mouse.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. The deterioration of subcellular organelles, including the mitochondria, is another major ultrastructural characteristic of AD pathogenesis, in addition to amyloid plaque deposition. However, the three-dimensional (3-D) study of mitochondrial structural alteration in AD remains poorly understood. Therefore, ultrastructural analysis, 3-D electron tomography, and immunogold electron microscopy were performed in the present study to clarify the abnormal structural alterations in mitochondria caused by the progression of AD in APP/PSEN1 transgenic mice, expressing human amyloid precursor protein, as a model for AD. Amyloid beta (A beta) plaques accumulated and dystrophic neurites (DN) developed in the hippocampus of transgenic AD mouse brains. We also identified the loss of peroxiredoxin 3, an endogenous cytoprotective antioxidant enzyme and the accumulation of A beta in the hippocampal mitochondria of transgenic mice, which differs from those in age-matched wild-type mice. The mitochondria in A beta plaque-detected regions were severely disrupted, and the patterns of ultrastructural abnormalities were classified into three groups: disappearance of cristae, swelling of cristae, and bulging of the outer membrane. These results demonstrated that morpho-functional alterations of mitochondria and AD progression are closely associated and may be beneficial in investigating the function of mitochondria in AD pathogenesis.
Division of Electron Microscopic Research, Korea Basic Science Institute, 169-148 Gwahangno, Yuseong-gu, Daejeon 305-806, Korea.
Ki Ju
KJ
Choi
Mi Jeong
MJ
Kim
A Reum
AR
Je
Sangmi
S
Jun
Chulhyun
C
Lee
Eunji
E
Lee
Mijung
M
Jo
Yang Hoon
YH
Huh
Hee-Seok
HS
Kweon
D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055032:Electron Microscope Tomography / Q000379:methods; D006624:Hippocampus / Q000473:pathology*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure*; D016501:Neurites / Q000473:pathology*; D061105:Peroxiredoxin III / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; C516116:Prdx3 protein, mouse; D053764:Presenilin-1; C580804:presenilin 1, mouse; D061105:Peroxiredoxin III