Tau progression in single severe frontal traumatic brain injury in human brains.

The neuropathological features of chronic traumatic encephalopathy (CTE), caused by repeated traumatic brain injury (TBI), include abnormal accumulations of hyper-phosphorylated tau (p-tau) protein in neurons, neurites and astrocytes, considered to progress via neuronal circuits in brains. Some previous reports suggest that a single severe TBI (sTBI) can also induce CTE and p-tau accumulation, but it is not clear whether the pathology is the same as that of repetitive TBI (rTBI). Since prefrontal leucotomy could be regarded as a model of sTBI, in this study we evaluated two autopsied schizophrenia with this procedure. Histopathologically, gliosis and neuronal loss were found not only in the primary ablated prefrontal region, but also in secondary affected areas, i.e., cingulate gyrus, medial nucleus of the thalamus, and nucleus accumbens, which are connected to prefrontal areas. Accumulation of p-tau was mostly seen in neurons, neurites and glias around small blood vessels in the leucotomized prefrontal region. In addition, secondary regions showed some p-tau-positive neurons/glias, as well as many axonal spheroids. Regions of neuronal/glial p-tau pathology showed immunoreactivity to both 3R/4R tau antibodies. Immunoblot analyses of sarkosyl-insoluble tau from frozen brains showed an AD-type tau banding pattern with strong immunoreactivities. sTBI patients showed limited comorbidities, such as TDP-43, alpha-synuclein or AD pathology, whereas rTBI patients have high frequencies of them. The findings suggest that p-tau in the primary affected lesion might progress to connected regions via neuronal circuits over time, and a single severe axonal injury might lead to CTE pathology different from that caused by rTBI.