As we move forward in our understanding of the underlying mechanisms of Alzheimer's disease, insights are constantly emerging from many different fronts. The disease is quite complex, and facts discerned by each new discovery must be assembled into an ever evolving theory. Sometimes, results that initially seem to be at odds with previous findings turn out to be integral to a clearer understanding of the disease.
In the field of Alzheimer research, there have been two competing hypotheses regarding the molecular basis of the pathology behind the disease: that of abnormal beta-amyloid metabolism in the brain versus abnromal tau protein processing. It is now believed by many that tau is affected downstream from an initial abnormality in beta-amyloid.
This week, research conducted at Washington University and published in the journal PLoS Genetics*, indicated a strong link between a specific genetic variant, a higher level of tau protein, and more rapid disease progression. These findings support the idea that tau proteins are a key driver of Alzheimer's pathology and imply that treatments targeting tau might delay disease progression. Not only has tau been shown to act downstream of Aß, several experiments have shown that cognition in mouse models can be improved by intervening at the level of tau.
This research may lead to new treatment targets with agents that regulate tau production; it may lead to diagnostic approaches to identify patients at risk of rapid progression; and it may lead to a more generally robust understanding of the entire pathological process of AD.
*Cruchaga C, Kauwe JS, Mayo K, Spiegel N, Bertelsen S, Nowotny P, Shah AR, Abraham R, Hollingworth P, Harold D, Owen MM, Williams J, Lovestone S, Peskind ER, Li G, Leverenz JB, Galasko D, Alzheimer’s Disease Neuroimaging Initiative, Morris JC, Fagan AM, Holtzman DM, Goate AM. SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer’s disease. PLoS Genetics. 2010 Sep 16;6(9).
Michael S. Rafii, M.D., Ph.D.
Associate Medical Director, Alzheimer's Disease Cooperative Study
This post originally appeared in Alzheimer's Insights, an ADCS Blog.