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(American Journal of Pathology. 1999;154:271-279.)
© 1999 American Society for Investigative Pathology

Regular Articles

Appearance of Sodium Dodecyl Sulfate-Stable Amyloid ß-Protein (Aß) Dimer in the Cortex During Aging

Miho Enya*|| , Maho Morishima-Kawashima* , Masahiro Yoshimura , Yasuhisa Shinkai , Kaoru Kusui*|| , Karen Khan§ , Dora Games§ , Dale Schenk§ , Shiro Sugihara¶ , Haruyasu Yamaguchi** and Yasuo Ihara*||

From the Department of Neuropathology,* Faculty of Medicine, University of Tokyo, Tokyo; the Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Kyoto; the Department of Neurology, Tokyo Women's Medical College, Tokyo; Athena Neurosciences Inc.,§ South San Francisco, California; the Department of Pathology,¶ Gunma Cancer Center, Ohta, Japan; Gunma University School of Health Sciences,** Maebashi, Japan; and Core Research for Evolutional Science and Technology,^|| Japan Science and Technology Corporation, Kawaguchi, Japan

We previously noted that some aged human cortical specimens containing very low or negligible levels of amyloid ß-protein (Aß) by enzyme immunoassay (EIA) provided prominent signals at 6~8 kd on the Western blot, probably representing sodium dodecyl sulfate (SDS)-stable Aß dimer. Re-examination of the specificity of the EIA revealed that BAN50- and BNT77-based EIA, most commonly used for the quantitation of Aß, capture SDS-dissociable Aß but not SDS-stable Aß dimer. Thus, all cortical specimens in which the levels of Aß were below the detection limits of EIA were subjected to Western blot analysis. A fraction of such specimens contained SDS-stable dimer at 6~8 kd, but not SDS-dissociable Aß monomer at ~4 kd, as judged from the blot. This Aß dimer is unlikely to be generated after death, because (i) specimens with very short postmortem delay contained the Aß dimer, and (ii) until 12 hours postmortem, such SDS-stable Aß dimer is detected only faintly in PDAPP transgenic mice. The presence of Aß dimer in the cortex may characterize the accumulation of Aß in the human brain, which takes much longer than that in PDAPP transgenic mice.

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