DOI: 10.1073/pnas.151261398. Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease

Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease

10.1073/pnas.151261398

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Active immunization with the amyloid β (Aβ) peptide has been shown to decrease brain Aβ deposition in transgenic mouse models of Alzheimer's disease and certain peripherally administered anti-Aβ antibodies were shown to mimic this effect. In exploring factors that alter Aβ metabolism and clearance, we found that a monoclonal antibody (m266) directed against the central domain of Aβ was able to bind and completely sequester plasma Aβ. Peripheral administration of m266 to PDAPP transgenic mice, in which Aβ is generated specifically within the central nervous system (CNS), results in a rapid 1,000-fold increase in plasma Aβ, due, in part, to a change in Aβ equilibrium between the CNS and plasma. Although peripheral administration of m266 to PDAPP mice markedly reduces Aβ deposition, m266 did not bind to Aβ deposits in the brain. Thus, m266 appears to reduce brain Aβ burden by altering CNS and plasma Aβ clearance.

Bibliography

DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001). Peripheral anti-AÎ² antibody alters CNS and plasma AÎ² clearance and decreases brain AÎ² burden in a mouse model of Alzheimerâs disease. Proceedings of the National Academy of Sciences, 98(15), 8850â8855.

Authors 6

Ronald B. DeMattos (first)
Kelly R. Bales (additional)
David J. Cummins (additional)
Jean-Cosme Dodart (additional)
Steven M. Paul (additional)
David M. Holtzman (additional)

References 35 Referenced 1,043

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 11:56 p.m.)
Indexed	1 week, 6 days ago (Aug. 19, 2025, 6:01 a.m.)
Issued	24 years, 1 month ago (July 3, 2001)
Published	24 years, 1 month ago (July 3, 2001)
Published Online	24 years, 1 month ago (July 3, 2001)
Published Print	24 years, 1 month ago (July 17, 2001)

Funders 0

None

BibTeX

@article{DeMattos_2001, title={Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer’s disease}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.151261398}, DOI={10.1073/pnas.151261398}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={DeMattos, Ronald B. and Bales, Kelly R. and Cummins, David J. and Dodart, Jean-Cosme and Paul, Steven M. and Holtzman, David M.}, year={2001}, month=jul, pages={8850–8855} }

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  "abstract": "<jats:p>Active immunization with the amyloid \u03b2 (A\u03b2) peptide has been shown to decrease brain A\u03b2 deposition in transgenic mouse models of Alzheimer's disease and certain peripherally administered anti-A\u03b2 antibodies were shown to mimic this effect. In exploring factors that alter A\u03b2 metabolism and clearance, we found that a monoclonal antibody (m266) directed against the central domain of A\u03b2 was able to bind and completely sequester plasma A\u03b2. Peripheral administration of m266 to PDAPP transgenic mice, in which A\u03b2 is generated specifically within the central nervous system (CNS), results in a rapid 1,000-fold increase in plasma A\u03b2, due, in part, to a change in A\u03b2 equilibrium between the CNS and plasma. Although peripheral administration of m266 to PDAPP mice markedly reduces A\u03b2 deposition, m266 did not bind to A\u03b2 deposits in the brain. Thus, m266 appears to reduce brain A\u03b2 burden by altering CNS and plasma A\u03b2 clearance.</jats:p>",
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