Nonselective PET radioligands, such as [18F]FDDNP (Shin et al., 2011), bind to both Aβ plaques and NFTs, and accurate quantitation of the amount of each protein present in many brain regions is not achievable. Hence, the field has sought to develop tau-selective PET radioligands that would complement existing Aβ-selective PET radioligands to image

AD, as well as presymptomatic SCR7 ic50 AD subjects (Morris et al., 2010 and Sperling et al., 2011). Such an agent would likely prove useful in following the clinical progression of AD, because NFT concentrations appear to reflect severity of clinical symptoms (Nagy et al., 1995), while Aβ plaques appear at an early (presymptomatic) stage and level off relatively early in the disease process (Hyman et al., 1993). An important use of tau-selective PET radiopharmaceuticals will be to assess tau load (or the loss or absence of tau load) in

anti-tau or anti-Aβ therapeutic clinical trials. Several clinical trials are under way to test the Aβ-cascade hypothesis in Aβ-positive cognitively normal subjects, and the addition of a tau-selective PET radioligand to Aβ-selective radioligands in these Dasatinib trials would provide additional important insights into the pathophysiology of AD. A tau-selective PET radioligand could potentially prove extremely useful in non-AD tauopathies as well. These include neurodegenerative diseases such as frontal temporal lobar degeneration (FTLD), Pick’s disease, corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). In their pure form, these dementias are characterized by tau deposits without the co-occurrence

of Aβ plaques. It is important to note that nearly tau deposits are of variable composition across these diseases. In AD, there are six different isoforms of hyperphosphorylated tau (varying in size from 352 to 441 amino acids). Three of the tau isoforms possess a three-repeat region, while three isoforms possess a four-repeat region. These repeat regions are believed to be responsible for the extended β-pleated sheet (amyloid) nature of these tau deposits. The various non-AD tauopathies contain differing combinations of these isoforms. If a tau-selective PET radioligand bound to all types of tau deposits, regardless of the combination of isoforms, it would find additional important uses in imaging the non-AD tauopathies. However, it is possible that a radioligand might bind well only to three-repeat tau isoforms and not be effective in imaging other tauopathies comprised mainly of four-repeat isoforms. For this reason, it is critical to assess the binding properties of the tau-selective radioligand to a variety of tau isoforms.