A paper in the January 17 Journal of Clinical Investigation online supports the idea that ABCA1 (ATP-binding cassette A1), a protein transporter involved in lipidation, can protect against amyloid buildup. David Holtzman and colleagues from Washington University, St. Louis, Missouri, overexpressed ABCA1 in PDAPP transgenic mice. First author Suzanne Wahrle and colleagues report that the mice have a very similar phenotype to ApoE-negative animals. Both ABCA1 overexpression and ApoE loss lead to significantly less amyloid-β in the hippocampus than normal PDAPP mice. What little Aβ is present occurs predominantly in the hilus. There is also a dearth of amyloid plaques, as judged by thioflavin S staining. Alzforum first discussed these findings in our report from the Bar Harbor Workshop, Enabling Technologies for Alzheimer Disease Research (see ARF related news story).

ABCA1 seems crucial for loading ApoE with lipid and loss of the transporter leads to reduced levels of ApoE, but not amyloid, in the brain (see ARF related news story). These latest results support the idea that the lipidation status of ApoE is intimately linked with its effect on Aβ processing and aggregation. The data “support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD,” write the authors.—Tom Fagan.

Reference:
Wahrle SE, Jiang H, Parsadanian M, Kim J, Li A, Knoten A, Jain S, Hirsch-Reinshagen V, Wellington CL, Bales KR, Paul SM, Holtzman DM. Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J. Clin. Invest. 2008 January 17 online. Abstract

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References

News Citations

  1. Enabling Technologies for Alzheimer Disease Research: Seventh Bar Harbor Workshop, 2007, Part 2
  2. ABCA1 Loss Lowers ApoE, Not Amyloid; New ApoE Immunology

Paper Citations

  1. . Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest. 2008 Feb;118(2):671-82. PubMed.

Further Reading

Papers

  1. . Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest. 2008 Feb;118(2):671-82. PubMed.

Primary Papers

  1. . Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease. J Clin Invest. 2008 Feb;118(2):671-82. PubMed.