Letter in response to Maderna E et al, Measles Inclusion‐Body Encephalitis: Neuronal Phosphorylated Tau Protein Is Present in the Biopsy but Not in the Autoptic Specimens of the Same Patient, Brain Pathology, doi: 10.1111/bpa.12332

We read the article “Measles Inclusion‐Body Encephalitis: Neuronal phosphorylated tau protein is present in the biopsy but not in the autoptic specimens of the same patient” with great interest 1. Maderna et al describe a case of Measles Inclusion‐Body Encephalitis (MIBE) in whom phospho‐tau deposition in the neuronal perikarya was observed in the brain biopsy sample but not in the autopsy tissues obtained a few days later. These findings are compared to those in Alzheimer's disease (AD) where phospho‐tau immunoreactivity does not differ between biopsy and autopsy specimens, and the possibility of phosphorylation being reversible when not associated with fibril formation is envisaged. Cerebrospinal fluid (CSF) total tau (t‐tau) and phosphorylated tau (p‐tau) levels were normal 1. Neuronal or glial fibrillary tangles have been shown in 20% of patients with subacute sclerosing panencephalitis (SSPE), another encephalitis caused by measles virus 2. We, therefore, reported CSF t‐tau, p‐tau and S100‐B levels in 60 newly diagnosed (<1 year of symptoms) SSPE and 31 neurological control patients 3. P‐tau levels were lower in the SSPE group (P = 0.009). This finding suggested no, or only scarce and immature, neurofibrillary pathology in early SSPE. Likewise, McQuaid et al observed no neurofibrillary tangles (NFT) in two SSPE cases with disease shorter than 1 year and numerous tau‐ and ubiquitin‐ positive tangles in disease longer than a few years 4. Early tangles, expected to predominate in MIBE because of the short period between the beginning of neurofibrillary changes and death, may be releasing lower amounts of tau to the CSF, explaining the CSF findings in 1. It is also possible that the chronic intracellular infection in SSPE affects the function of kinases phosphorylating tau, while the activity of viral kinases is more prominent in MIBE, as discussed by the authors.

Elevated t‐tau in neurodegenerative diseases reflects axonal and neuronal degeneration, and p‐tau, NFT formation. CSF t‐tau and p‐tau levels are elevated in AD. Conversely, t‐tau is elevated while p‐tau is not increased in Creutzfeldt–Jakob disease which, unlike AD, is not associated with NFT 5, 6. The normal CSF p‐tau level in MIBE suggests NFT formation is not among key pathologic processes in this disorder 1.