| Abstract | 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. |
| Authors | K Noda-Saita, A Yoneyama, Y Shitaka, Y Hirai, K Terai, J Wu, T Takeda, K Hyodo, N Osakabe, T Yamaguchi, M Okada
(Affiliation: Neuroscience, Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21, Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kyouko.saita at jp.astellas.com)
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| Journal | Neuroscience
(Neuroscience)
Vol. 138
Issue 4
Pg. 1205-13
( 2006)
ISSN: 0306-4522 United States |
| PMID | 16460878
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Amyloid beta-Protein
- Peptide Fragments
- amyloid beta-protein (1-40)
- amyloid beta-protein (1-42)
|
| Topics |
- Aging
(pathology)
- Alzheimer Disease
(physiopathology, radiography)
- Amyloid beta-Protein
(metabolism)
- Animals
- Cerebral Cortex
(metabolism, pathology, radiography)
- Disease Models, Animal
- Female
- Mice
- Mice, Transgenic
- Microscopy, Phase-Contrast
(methods)
- Neurites
(metabolism, pathology)
- Peptide Fragments
(metabolism)
- Predictive Value of Tests
- Senile Plaques
(metabolism, pathology, radiography)
- Tomography, X-Ray Computed
(methods)
|
