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Untangling a deadly conspiracy

With tau's aid, ß-amyloid spurs the cells' microtubule network (white) to crumble (bottom).

King et al. reveal on page 541 how tau and ß-amyloid might collaborate to spark the cellular devastation of Alzheimer's disease (AD). The findings suggest that the two rogue proteins team up to break down the microtubules that enable neurons to deliver necessities to their axons.

AD's hallmarks are ß-amyloid plaques that pile up outside of neurons and tangles of tau that amass inside. How the two proteins interact remains mysterious, but previous work indicates that ß-amyloid lies upstream of tau in the cell damage pathway.

To clarify the connection, King et al. engineered kidney cells to pump out tau. In neurons from AD patients, microtubules collapse. The researchers saw the same effect when they dosed their engineered kidney cells with Aß42, a particularly destructive version of ß-amyloid.

Individual ß-amyloid molecules can link together into long, tough fibrils that are prevalent in plaques. The cells were impervious to this fibrous form of ß-amyloid, however, supporting the hypothesis that fibrils represent the brain's attempt to incarcerate ruinous ß-amyloid.

Aß42 also triggered microtubule breakdown in neurons, but not if the researchers first blocked tau with RNAi. The scientists now want to decipher how ß-amyloid prods tau to do its bidding to cause microtubule collapse. Breaking down microtubules might harm neurons by interfering with the transport of essential cargo into axons and delivery of patches to fill gaps in the cell membrane.

Mitch Leslie

mitchleslie{at}comcast.net

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Related Article

Tau-dependent microtubule disassembly initiated by prefibrillar ß-amyloid

Michelle E. King, Ho-Man Kan, Peter W. Baas, Alev Erisir, Charles G. Glabe, and George S. Bloom
J. Cell Biol. 2006 175: 541-546. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 1141K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Leslie, M. Search for Related Content PubMed Articles by Leslie, M. Related Collections Related Article Social Bookmarking                            What's this?