Quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease by phase-contrast X-ray computed tomography.
Densely aggregated beta-amyloid peptides are believed to play a key role in the pathogenesis of Alzheimer's disease. Amyloid plaques are a potential target for molecular imaging to determine the clinical status of Alzheimer's disease. Phase-contrast X-ray imaging combined with computed tomography is a promising technique that can be used to visualize the physical density of structures in biological tissues non-invasively, and without the use of imaging agents. Using brain tissue isolated from a mouse model of Alzheimer's disease, we show that beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques, but not beta-amyloid 40-negative/beta-amyloid 42-positive amyloid plaques, exist as high-density aggregates that can be specifically detected by phase-contrast X-ray computed tomography. The phase-contrast X-ray computed tomography detected beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques in three-dimensions with an extremely high sensitivity comparable to that of histological analysis, and also enabled the load of amyloid plaques to be quantified. Furthermore, the use of phase-contrast X-ray computed tomography reveals that the physical density of beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques increases with age, and that the large volume, high-density, amyloid plaques that are specifically observed in aged Alzheimer's disease mice are closely associated with neuritic dystrophy. These results demonstrate that phase-contrast X-ray computed tomography is a highly sensitive imaging technique for analyzing dense-cored amyloid plaques in postmortem samples, and is beneficial in elucidating amyloid pathophysiology in Alzheimer's disease.
Noda-Saita
K
K
Neuroscience, Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kyouko.saita@jp.astellas.com
Yoneyama
A
A
Shitaka
Y
Y
Hirai
Y
Y
Terai
K
K
Wu
J
J
Takeda
T
T
Hyodo
K
K
Osakabe
N
N
Yamaguchi
T
T
Okada
M
M
D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D008858:Microscopy, Phase-Contrast / Q000379:methods; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D011237:Predictive Value of Tests; D014057:Tomography, X-Ray Computed / Q000379:methods*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)