High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice

Ken Ichiro Fukuchi, Libin Ho, Steven G Younkin, Dennis D. Kunkel, Charles E. Ogburn, Renee C. LeBoeuf, Clement E. Furlong, Samir S. Deeb, David Nochlin, Jerzy Wegiel, Henry M. Wisniewski, George M. Martin

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Abstract

We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human β-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick β-actin promoter. There were exceptionally high levels of β- amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral β- amyloidosis despite extremely high levels of circulating β-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of β-amyloid precursor protein may play a predominant role in cerebral β- amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)219-227
Number of pages9
JournalAmerican Journal of Pathology
Volume149
Issue number1
StatePublished - Jul 1996

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Amyloid
Transgenic Mice
Peptides
Amyloid beta-Protein Precursor
Amyloidosis
Protein Sorting Signals
Amyloid angiopathy
Cytomegalovirus
Transgenes
Intestines
Actins
Amino Acids

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Fukuchi, K. I., Ho, L., Younkin, S. G., Kunkel, D. D., Ogburn, C. E., LeBoeuf, R. C., ... Martin, G. M. (1996). High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice. American Journal of Pathology, 149(1), 219-227.

High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice. / Fukuchi, Ken Ichiro; Ho, Libin; Younkin, Steven G; Kunkel, Dennis D.; Ogburn, Charles E.; LeBoeuf, Renee C.; Furlong, Clement E.; Deeb, Samir S.; Nochlin, David; Wegiel, Jerzy; Wisniewski, Henry M.; Martin, George M.

In: American Journal of Pathology, Vol. 149, No. 1, 07.1996, p. 219-227.

Research output: Contribution to journalArticle

Fukuchi, KI, Ho, L, Younkin, SG, Kunkel, DD, Ogburn, CE, LeBoeuf, RC, Furlong, CE, Deeb, SS, Nochlin, D, Wegiel, J, Wisniewski, HM & Martin, GM 1996, 'High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice', American Journal of Pathology, vol. 149, no. 1, pp. 219-227.
Fukuchi, Ken Ichiro ; Ho, Libin ; Younkin, Steven G ; Kunkel, Dennis D. ; Ogburn, Charles E. ; LeBoeuf, Renee C. ; Furlong, Clement E. ; Deeb, Samir S. ; Nochlin, David ; Wegiel, Jerzy ; Wisniewski, Henry M. ; Martin, George M. / High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice. In: American Journal of Pathology. 1996 ; Vol. 149, No. 1. pp. 219-227.
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