By Rudy Tanzi | Chair, Research Consortium
The New York Times has a front-page story on the spreading of Tau
pathology from neuron to neuron, citing papers from the laboratories of Dr.
Brad Hyman of Massachusetts General Hospital and Dr. Karen Duff of Columbia
University. Cure Alzheimer's Fund has been supporting key research along
these lines over the past two years, and is playing a major role going forward.
Alzheimer's has two famous hallmarks: Abeta peptide "plaques" outside of
brain cells and Tau "tangles" inside the cells. In its healthy mode, the Tau
protein provides "scaffolding" for cell structure. In its pathogenic mode, it forms
into tangles which eventually choke and kill the cell.
In 2009, evidence first emerged suggesting that Tau pathology (tangles)
spreads from neuron to neuron. Our research, and increasingly that of others, shows
that Abeta and Tau work together to initiate Alzheimer's disease. The pathology
appears to begin with excess clumps of Abeta called oligomers which then
initiate tauopathy (tangles). The tauopathy then spreads from nerve cell to
nerve cell.
The first papers showing that tauopathy spreads from neuron to neuron were
published in 2009:
Propagation of tau misfolding from the outside to the inside of a cell
Frost B, Jacks RL, Diamond MI.
J. Biol. Chem. 2009 284 (11): 12845-12852. Epub 2009 March 11.
Transmission and spreading of tauopathy in transgenic mouse brain.
Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A,
Fraser G, Stalder AK, Beibel M, Staufenbiel M, Jucker M, Goedert M, Tolnay M.
Nat Cell Biol. 2009 Jul;11(7):909-13. Epub 2009 Jun 7.
The 2009 studies initially met with the expected amount of skepticism, but
were later confirmed by other groups, including that of Dr. Virginia Lee at the
University of Pennsylvania in her Spring 2011 paper:
Seeding of normal Tau by pathological Tau conformers drives pathogenesis of
Alzheimer-like tangles.
Guo JL, Lee VM.
J Biol Chem. 2011 Apr 29;286(17):15317-31. Epub 2011 Mar 3.
After Dr. Lee confirmed the initial studies Cure Alzheimer's Fund began
supporting studies of spreading tauopathy in her lab. Her subsequent
research has built much of the framework for the studies cited in the New York Times
article.
In recent presentations I have been referring to AD as a "beta-amyloid
triggered tauopathy". Genetic studies show that AD begins with excess accumulation of
beta-amyloid, but pathology-based studies show that tangles are needed for
dementia. If the initial accumulation of excess Abeta in the brain can be
stopped, the tauopathy can be nipped in the bud. But once tauopathy starts,
both Abeta and Tau need to be attacked because the tauopathy will keep spreading
to new brain regions. This is the new paradigm Dr. Lee has been investigating
with Cure Alzheimer's support.
Cure Alzheimer's Fund will also soon be funding important new research by
Dr. Dennis Selkoe and Dr. Dominic Walsh of Brigham and Women's Hospital in
Boston on complementary Tau protein work and the role of Abeta oligomers in driving
tangle formation.
Taken together, all of these studies are giving us a much more vivid -- and
target-rich -- picture of Alzheimer's disease.
Project reports on GlobalGiving are posted directly to globalgiving.org by Project Leaders as they are completed, generally every 3-4 months. To protect the integrity of these documents, GlobalGiving does not alter them; therefore you may find some language or formatting issues.
If you donate to this project or have donated to this project, you can receive an email when this project posts a report. You can also subscribe for reports without donating.
Support this important cause by creating a personalized fundraising page.
Start a Fundraiser
