NEW FINDINGS REGARDING TAU PROTEIN PROVIDE INSIGHT INTO ALZHEIMER'S PATHOGENESIS

To date, a thorough understanding of how Alzheimer’s develops and progresses has remained elusive.  It has long been thought that a protein known as 'tau' is directly involved in Alzheimer's pathogenesis, but the specific role of tau has not been well understood.  Tau protein is present within the brain of individuals who do not have Alzheimer’s, and in this context appears to promote the healthy functioning of neurons.  However, abnormal forms of tau protein aggregate inside cells within the brains of individuals suffering from Alzheimer’s, forming the ‘neurofibrillary tangles’ that are characteristic of the disease. 

Last week, The New York Times announced that two different research studies have generated important findings indicating that tau may be responsible for the spread of Alzheimer's disease throughout various regions of the brain.  In one of these studies, which was led by Karen Duff and colleagues of Columbia University’s Taub Institute for Alzheimer’s Disease Research, researchers observed that, over time, ‘tau pathology’ (or ‘tauopathy’) does not arise independently within different regions of the brain; instead, it spreads from its initial site within the brain’s entorhinal cortex to neurons within other regions of the brain, directly through the synaptic connections between individual neurons.  While the mechanisms underlying this are not yet well understood, the researchers note that these findings - published in the open-access journal PLos One - provide a great deal of insight into Alzheimer's pathogenesis, demonstrating that:

AD progresses via an anatomical cascade as opposed to individual events occurring in differentially vulnerable regions.  [PLos One]

The New York Times describes a second study, soon-to-be-published in the journal Neuron, conducted by a team of researchers led by Bradley T. Hyman of the Alzheimer’s Disease Research Center at Massachusetts General Hospital.  Like Duff et al., these researchers observed that, over time, abnormal tau protein spreads from the entorhinal cortex to other regions within the brain via some sort of direct neuronal connection, rather than arising independently within each region - thereby representing the pathway by which Alzheimer's spreads throughout the brain.  It therefore can be postulated that agents capable of blocking this pathway may be effective in blocking the progression of Alzheimer's disease. 

Additional findings regarding the potential role that tau protein may play in Alzheimer’s have been generated by a third team of researchers.  Led by Rakez Kayed of the University of Texas Medical Branch at Galveston, and reported in the FASEB Journal, these researchers have determined that an intermediate form of tau appears to be more highly toxic than either single units of the protein or the larger neurofibrillary tangles.  These intermediates are comprised of ‘tau oligomers’; that is, aggregates of a small number of individual units of tau protein.  Also referred to as ‘prefilamentous tau aggregates’, these oligomeric intermediates are found in significantly greater levels within the Alzheimer’s brain than in healthy brains.  The researchers conclude that these tau oligomers - which ultimately join together to form neurofibrillary tangles - appear to represent the most highly toxic entities associated with the progression of Alzheimer's disease, and therefore may represent important therapeutic targets.