Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models.

Yona Levites, Lisa A. Smithson, Robert W. Price, Rachel S. Dakin, Bin Yuan, Michael R. Sierks, Jungsu Kim, Eileen McGowan, Kim Reed Dana, Terrone L. Rosenberry, Pritam Das, Todd E. Golde

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

A number of hypotheses regarding how anti-Abeta antibodies alter amyloid deposition have been postulated, yet there is no consensus as to how Abeta immunotherapy works. We have examined the in vivo binding properties, pharmacokinetics, brain penetrance, and alterations in Abeta levels after a single peripheral dose of anti-Abeta antibodies to both wild-type (WT) and young non-Abeta depositing APP and BRI-Abeta42 mice. The rapid rise in plasma Abeta observed after antibody (Ab) administration is attributable to prolongation of the half-life of Abeta bound to the Ab. Only a miniscule fraction of Ab enters the brain, and despite dramatic increases in plasma Abeta, we find no evidence that total brain Abeta levels are significantly altered. Surprisingly, cerebral spinal fluid Abeta levels transiently rise, and when Ab:Abeta complex is directly injected into the lateral ventricles of mice, it is rapidly cleared from the brain into the plasma where it remains stable. When viewed in context of daily turnover of Abeta, these data provide a framework to evaluate proposed mechanisms of Abeta attenuation mediated by peripheral administration of an anti-Abeta monoclonal antibody (mAb) effective in passive immunization paradigm. Such quantitative data suggest that the mAbs are either indirectly enhancing clearance of Abeta or targeting a low abundance aggregation intermediate.

Original languageEnglish (US)
Pages (from-to)2576-2578
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume20
Issue number14
DOIs
StatePublished - Dec 2006

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Anti-Idiotypic Antibodies
Alzheimer Disease
Antibodies
Brain
Life Support Care
Plasmas
Passive Immunization
Penetrance
Lateral Ventricles
Amyloid
Immunotherapy
Immunization
Half-Life
Consensus
Pharmacokinetics
Monoclonal Antibodies
Agglomeration
Fluids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models. / Levites, Yona; Smithson, Lisa A.; Price, Robert W.; Dakin, Rachel S.; Yuan, Bin; Sierks, Michael R.; Kim, Jungsu; McGowan, Eileen; Dana, Kim Reed; Rosenberry, Terrone L.; Das, Pritam; Golde, Todd E.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 20, No. 14, 12.2006, p. 2576-2578.

Research output: Contribution to journalArticle

Levites, Y, Smithson, LA, Price, RW, Dakin, RS, Yuan, B, Sierks, MR, Kim, J, McGowan, E, Dana, KR, Rosenberry, TL, Das, P & Golde, TE 2006, 'Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models.', The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 20, no. 14, pp. 2576-2578. https://doi.org/10.1096/fj.06-6463fje
Levites, Yona ; Smithson, Lisa A. ; Price, Robert W. ; Dakin, Rachel S. ; Yuan, Bin ; Sierks, Michael R. ; Kim, Jungsu ; McGowan, Eileen ; Dana, Kim Reed ; Rosenberry, Terrone L. ; Das, Pritam ; Golde, Todd E. / Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer's disease mouse models. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006 ; Vol. 20, No. 14. pp. 2576-2578.
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