It is interesting that Tau13 was unable to readily detect pathology in CBD, PSP, and CTE because it did effectively label pathology in PiD and AD, even if the amount of parenchymal tau staining often obscured some of the less intense staining.18 Tau13 is a remarkably sensitive tau antibody with no previously demonstrated changes to affinity because of alterations in tau. tau varieties and showed a range of performance at identifying tau pathologies in the non-AD tauopathies. These findings demonstrate the conformational display of the PAD in tau represents a common pathological event in many tauopathies. Dysfunction and aggregation of the tau protein are hallmarks of the group of neurodegenerative disorders known as tauopathies. Some of the diseases included in this group are Alzheimer disease (AD), Pick out disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). Although tau aggregation is definitely a dominating neuropathological phenotype of these diseases, the morphology of these aggregates, the cell types affected, and/or their locations within the brain vary between diseases.1 For instance, in AD, tau pathology is 1st observed in the transentorhinal region before appearing in the hippocampus and then neocortical areas as the disease progresses.2 The dominant pathology takes the form of flame-shaped AZD1981 neurofibrillary tangles, neuropil threads, and neuritic plaques.3 Each of the AZD1981 non-AD tauopathies are differentiated by specific pathognomonic inclusions (as well as clinical presentations and mind regions affected) Tap1 that include not only neuronal but also primarily glial lesions in some diseases.4 PiD is characterized by the presence of Pick bodies, spherical tau inclusions located within neurons of the dentate gyrus of the hippocampus as well as with the frontal and temporal cortices, in addition to some tau aggregation in glia.5, 6 AZD1981 PSP displays neuronal tau pathology in the form of round or globose tangles, along with neuropil threads.7 In addition, tau pathology is present in glial cells, in the form of extensive tufted astrocytes and oligodendrocytic coiled bodies.8, 9 In CBD, tau pathology is characterized by prominent astrocytic plaques along with occasional coiled body and neuronal inclusions.10 Similarly, CTE tau lesions affect both neurons and glial cells in the frontal and temporal cortices, particularly in perivascular regions and at the depths of sulci, as well as with limbic areas and the brainstem.11, 12 The pathological inclusions found in the various tauopathies are associated with conformation changes resulting in misfolded forms of tau. Antibodies such as Alz50 and MC1 identify discontinuous, conformation-specific tau epitopes and provide evidence that these changes in conformation are early markers for the protein’s dysfunction in disease and precede the formation of classic neurofibrillary tangles in AD.13, 14, 15, 16 Previously, we demonstrated that specific antibodies directed toward the amino terminus of tau (ie, TNT1 and TNT2) were effective at differentiating pathogenic forms of tau from normal forms of the protein in AD post-mortem brain cells.17, 18 In contrast, other antibodies with nearby N-terminal epitopes (ie, Tau12 and Tau13) were unable to differentiate between normal and pathological forms of tau, indicating the conformational changes could be relatively subtle and confined to the TNT1 and TNT2 epitopes (eg, within amino acids 7 to 12). More important, we have demonstrated the conformational changes recognized by these antibodies may directly mediate the toxicity associated with pathological forms of the protein. The region of tau recognized from the TNT antibodies is located within the 1st 18 amino acids of the protein, AZD1981 in a region described as the phosphatase-activating website (PAD).17 In pathogenic forms of the protein (eg, aggregated AZD1981 tau or tau phosphorylated at particular epitopes), this region is aberrantly exposed, leading to a disruption of kinesin-based anterograde fast axonal transport.17, 19, 20, 21 Exposure of this motif.