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(American Journal of Pathology. 2001;158:2209-2218.)
© 2001 American Society for Investigative Pathology

Regular Article

Accumulation of Amyloid ß-Protein in the Low-Density Membrane Domain Accurately Reflects the Extent of ß-Amyloid Deposition in the Brain

Noriko Oshima^*, Maho Morishima-Kawashima^*, Haruyasu Yamaguchi, Masahiro Yoshimura, Shiro Sugihara^¶, Karen Khan^||, Dora Games^||, Dale Schenk^|| and Yasuo Ihara^*

From the Department of Neuropathology,^*
Faculty of Medicine, University of Tokyo, Tokyo, Japan; the Core Research for Evolutional Science and Technology,
Japan Science and Technology Corporation, Kawaguchi, Japan; the Gunma University School of Health Sciences,
Maebashi, Japan; the Kyoto Prefectural University of Medicine,
Kyoto, Japan; the Gunma Cancer Center,^¶
Ohta, Japan; and Elan Pharmaceuticals,^||
South San Francisco, California

To learn more about the process of amyloid ß-protein (Aß) deposition in the brain, human prefrontal cortices were fractionated by sucrose density gradient centrifugation, and the Aß content in each fraction was quantified by a two-site enzyme-linked immunosorbent assay. The fractionation protocol revealed two pools of insoluble Aß. One corresponded to a low-density membrane domain; the other was primarily composed of extracellular Aß deposits in those cases in which Aß accumulated to significant levels. Aß42 levels in the low-density membrane domain were proportional to the extent of total Aß42 accumulation, which is known to correlate well with overall amyloid burden. In PDAPP mice that form senile plaques and accumulate Aß in a similar manner to aging humans, Aß42 accumulation in the low-density membrane domain also increased as Aß deposition progressed with aging. These observations indicate that the Aß42 associated with low-density membrane domains is tightly coupled with the process of extracellular Aß deposition.

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