Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, Shankle WR, Elizarov A, Kolb HC.
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F-18]-T807.
J Alzheimers Dis. 2013 Jan 1;34(2):457-68.
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Imaging tau during life represents the next frontier of AD neuroimaging. We know from autopsy studies that cognitive symptoms in AD correlate much more strongly with the distribution and burden of neurofibrillary tangles than with amyloid plaques. Many have speculated that, while plaques may play an important role early in the disease, it is the tangles that drive the loss of brain tissue that ultimately leads to memory loss and other symptoms.
Understanding the relationships between Aβ and tau may be critical for developing therapies, but has proven challenging because most animal models of AD (that are based on human mutations that drive Aβ overproduction) lead to plaques but not tangles. Just as amyloid imaging has shed light on the effects of amyloid on the human brain, tau imaging would give us a much more complete picture of how the two proteins interact with the brain and each other, and ultimately lead to disease.
There is also likely to be an influx of putative tau-based therapies in the coming years. If it is true that amyloid plays an early role but tangles drive the symptoms, then targeting tau may be a good strategy for treating the symptomatic phase of AD. Having an imaging marker would greatly facilitate the development of these drugs.
Finally, tau is the primary protein that accumulates in the brain in other brain diseases like frontotemporal dementia, corticobasal degeneration, progressive supranuclear palsy, and, most recently, chronic traumatic encephalopathy, the degenerative disease associated with repeated mild traumatic brain injury that affects pro athletes and military veterans.
Tau imaging is the vertical advance the field needs as we move from diagnosing and treating dementia based on symptoms to an era in which we detect and target our therapy towards specific toxic protein aggregates.