Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease.

Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Research Abstract Details 

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Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Abstract Text:

Martin J Sadowski,Joanna Pankiewicz,Henrieta Scholtzova,Pankaj D Mehta,Frances Prelli,David Quartermain,Thomas Wisniewski,

The amyloid-beta (Abeta) cascade hypothesis of Alzheimer's disease (AD) maintains that accumulation of Abeta peptide constitutes a critical event in the early disease pathogenesis. The direct binding between Abeta and apolipoprotein E (apoE) is an important factor implicated in both Abeta clearance and its deposition in the brain's parenchyma and the walls of meningoencephalic vessels as cerebral amyloid angiopathy. With the aim of testing the effect of blocking the apoE/Abeta interaction in vivo as a potential novel therapeutic target for AD pharmacotherapy, we have developed Abeta12-28P, which is a blood-brain-barrier-permeable nontoxic, and nonfibrillogenic synthetic peptide homologous to the apoE binding site on the full-length Abeta. Abeta12-28P binds with high affinity to apoE, preventing its binding to Abeta, but has no direct effect on Abeta aggregation. Abeta12-28P shows a strong pharmacological effect in vivo. Its systemic administration resulted in a significant reduction of Abeta plaques and cerebral amyloid angiopathy burden and a reduction of the total brain level of Abeta in two AD transgenic mice models. The treatment did not affect the levels of soluble Abeta fraction or Abeta oligomers, indicating that inhibition of the apoE/Abeta interaction in vivo has a net effect of increasing Abeta clearance over deposition and at the same time does not create conditions favoring formation of toxic oligomers. Furthermore, behavioral studies demonstrated that treatment with Abeta12-28P prevents a memory deficit in transgenic animals. These findings provide evidence of another therapeutic approach for AD.

Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Publishing Authors By Initials

MJ Sadowski,J Pankiewicz,H Scholtzova,PD Mehta,F Prelli,D Quartermain,T Wisniewski,

For similar peptides: peptide fragments research abstracts see: peptides: peptide fragments research

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Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 18787-92

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 20

MONTH: 11

YEAR: 2006

Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Keywords Mesh Terms:

KEYWORDS: Peptide Fragments

MESH TERMS: metabolism

Chemical & Substance for Abstract: Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease. Information

Substance Name: amyloid beta-protein (12-28)

Registry Number: 0

Grant and Affiliation Information for Blocking the apolipoprotein E/amyloid-beta interaction as a potential therapeutic approach for Alzheimer's disease.

AFFILIATION: Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. sadowm01@med.nyu.edu

Country: United States

AGENCY: United States NIA

GRANT: AG 20747

ACRONYM: AG

MEDLINETA: Proc Natl Acad Sci U S A

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