We thank Dr. Yuksel and coworkers for their interest in our neuropathological and immunohistochemical study of a case of measles inclusion‐body encephalitis (MIBE) and take the opportunity to further discuss the remarkable issue of tau modifications in neurodegenerative diseases and other neurological pathologic conditions.
The main finding of our work was that in the MIBE patient who we examined, immunohistochemistry for phosphorylated tau protein (phospho‐tau) in the cerebral biopsy differed substantially from those obtained in the autopsy tissue performed few days later. Although neurofibrillary tangles (NFT) were not present, marked immuno‐positivity for phospho‐tau under the form of diffuse perikaryal and rosary‐bead dendritic labeling was detected in the bioptic tissue, but was absent in the autoptic material. Our interpretation was that tau phosphorylation was at an early stage, not associated with modifications of the conformation of tau protein and, therefore, could be reversed by phosphatases acting in the interval between death and sampling of the brain at autopsy.
Subacute sclerosing pan‐encephalitis (SSPE), a chronic measles virus infection of the CNS, and MIBE that occurs in immuno‐compromised individuals and has a rapidly progressive course share the etiologic agent, as neuronal inclusions made up of measles virus are present in both.
In their letter, Yuksel and coworkers underline how NFT made up of phospho‐tau are present in a limited percentage (about 20%) of SSPE cases, concluding that NFT formation is not among key pathologic processes in SSPE.
The fact that CSF levels of total tau and phospho tau are normal in SSPE, is in agreement with this view, however, it should be considered that although tau and especially phospho‐tau CSF levels are considered markers of NFT and tauopathy, studies demonstrating this correlation by a comparative analysis of CSF and brain tissue are lacking.
The normal CSF phospho‐tau level in our MIBE case in the presence of phospho‐tau cerebral depositions is in line with a limited sensitivity of the CSF increase of phospho‐tau levels as markers of cerebral phospho‐tau deposition, at least in some settings.
Moreover, if we assume that, in analogy with MIBE, in SSPE abnormal phospho‐tau deposition could occur mostly under the form of pretangles that is not organized in the abnormal insoluble filaments of NFT, it is conceivable that also in SSPE the percentage of positive cases for neuronal phospho‐tau would be higher if analyzed by cerebral biopsy rather than screened using autoptic tissue.
Many aspects of the pathogenetic mechanisms leading to tau changes in neurodegeneration and in the other conditions in which they occur remain to be clarified, and hopefully future studies of comparison of biopsy vs. autopsy findings may contribute to shed light on this issue.
In any case, our observation indicates that autopsy findings are not always overlapping with the results obtained in those rare instances in which the cerebral tissue can be analyzed without the modifications that post mortem interval and terminal agonal state invariably cause.