Identical tau filaments in subacute sclerosing panencephalitis and chronic traumatic encephalopathy.

Subacute sclerosing panencephalitis (SSPE) occurs in some individuals after measles infection, following a symptom-free period of several years. It resembles chronic traumatic encephalopathy (CTE), which happens after repetitive head impacts or exposure to blast waves, following a symptom-free period. As in CTE, the neurofibrillary changes of SSPE are concentrated in superficial cortical layers. Here we used electron cryo-microscopy (cryo-EM) of tau filaments from two cases of SSPE to show that the tau folds of SSPE and CTE are identical. Two types of filaments were each made of two identical protofilaments with an extra density in the ß-helix region. Like in CTE, the vast majority of tau filaments were Type I, with a minority of Type II filaments. These findings suggest that the CTE tau fold can be caused by different environmental insults, which may be linked by inflammatory changes.

Neuropathological studies of serotonergic and noradrenergic systems in Lewy body disease patients with delusion or depression.

AIM: The association between psychiatric symptoms in Lewy body disease (LBD) and the noradrenergic and serotonergic systems is still controversial. This study investigated the quantitative relationships of depression and delusion with these systems. METHODS: We studied 24 postmortem tissues from individuals with a pathological diagnosis of LBD with sufficient clinical history. The numbers of neurons and Lewy bodies (LBs) in the locus coeruleus (LC) and dorsal raphe nucleus (DRN) were counted, and the density of neurons in the DRN was analyzed. In addition, the densities of tryptophan hydroxylase-positive neurites and norepinephrine transporter-positive neurites in the amygdala and dorsal prefrontal cortex were measured. Finally, we divided the cases into two groups: with or without depressive mood, and with or without delusion. Quantitative histological data were compared between the groups. RESULTS: The group with depressive mood had a significantly smaller number of neurons in the LC compared with the group without depressive mood. The group with delusion had a significantly larger number of LBs in the DRN compared with the group without delusion. The density of norepinephrine transporter-positive neurites in the dorsal prefrontal cortex was significantly correlated with the number of neurons in the LC. CONCLUSIONS: The accumulation of LBs in the DRN of individuals with LBD was associated with delusion, whereas a decrease in the number of neurons in the LC was associated with depressive mood. These neurodegenerative changes involved the serotonergic and noradrenergic systems and may be associated with the formation of delusion and depression, respectively, in LBD.

Pathologically Verified Corticobasal Degeneration Mimicking Richardson's Syndrome Coexisting with Clinically and Radiologically Shunt-Responsive Normal Pressure Hydrocephalus.

Background: Normal pressure hydrocephalus (NPH) manifests as gait instability, cognitive impairment, and urinary incontinence. This clinical triad of NPH sometimes occurs with ventriculomegaly in patients with neurodegenerative disease. Patients with pathologically verified neurodegenerative diseases, such as progressive supranuclear palsy (PSP), have received antemortem diagnoses of NPH. Objectives: This study presents clinical and pathological features of a patient with pathologically verified corticobasal degeneration (CBD) coexisting with clinically shunt-responsive NPH. Methods: We performed clinical, radiological, and pathological evaluations in a patient with CBD whose antemortem diagnosis was PSP Richardson's syndrome (PSP-RS) coexisting with shunt-responsive NPH. Results: A 59-year-old woman developed bradykinesia and gait instability and then frequent falls, urinary incontinence, and supranuclear vertical gaze palsy followed. At 63 years of age, her gait disturbance and urinary incontinence had deteriorated rapidly, and cognitive impairment was disclosed. There were typical findings of NPH with ventriculomegaly and disproportionately enlarged subarachnoid space hydrocephalus as well as a 2-layer appearance with decreased and increased cerebral blood perfusion. Shunt placement ameliorated gait instability for more than 1 year and improved radiological indicators of NPH. However, atrophy of the midbrain progressed with time after transient increases in size. Although the antemortem diagnosis was probable PSP-RS, pathological evaluation verified CBD. There were severe discontinuities of the ependymal lining of the lateral ventricles and subependymal rarefaction and gliosis with tau-positive deposition. Conclusions: Shunt surgery could ameliorate NPH symptoms in patients with 4-repeat tauopathies. Careful assessments of clinical findings are necessary to predict the benefits of shunts as a therapeutic option for patients with neurodegenerative diseases coexisting with NPH.

Pathologic and Neuropathologic Study of a Case of COVID-19.

A 68-year-old woman with a history of schizophrenia developed coronavirus disease (COVID)-19 and was transferred to our hospital. Despite treatment, she died of respiratory failure 16 days after the onset. At the time of autopsy, polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA using swabs from the nasopharynx and the lung was positive; however, the cerebrospinal fluid was negative. An autopsy showed diffuse alveolar damage and recent multiple cerebral infarcts. Acute splenitis was observed with thrombi adhering to the vascular endothelium in areas of severe neutrophilic infiltration. Immunohistochemistry using an antibody against the SARS-CoV-2 nucleocapsid showed immunoreactivity along the hyaline membrane of the lung; however, the antibody showed no immunoreactivity in the medulla, the thalamus, the frontal lobe, and the pituitary. Future pathologic studies should clarify the mechanisms involved in a variety of clinical and pathological changes related to COVID-19.

Histopathological validation and clinical correlates of hippocampal subfield volumetry based on T2-weighted MRI in temporal lobe epilepsy with hippocampal sclerosis.

The objectives of this study were 1) to histologically validate the hippocampal subfield volumetry based on T2-weighted MRI, and 2) to explore its clinical impact on postsurgical memory function and seizure outcome in temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). We analyzed the cases of 24 patients with medial TLE (12 left, 12 right) and HS who were preoperatively examined with T2-weighted high-resolution MRI. The volume of each hippocampal subfield was calculated with an automatic segmentation of hippocampal subfields (ASHS) program. Hippocampal sclerosis patterns were determined pathologically, and the cross-sectional area and neuronal cell density of the CA1 and CA4 subfields were calculated using tissue specimens. Pre- and postoperative memory evaluations based on the Wechsler Memory Scale-Revised (WMS-R) were performed. We compared the presurgical MRI-based volumes with the pathological measurements in each subfield and then compared them with the change in the patients' neurocognitive function. As a result, there was a significant relationship between the presurgical MRI-based volume of CA4/dentate gyrus (DG) and the cross-sectional area of CA4 calculated with tissue specimens (Spearman's rs = 0.482, p = 0.023), and a similar trend-level correlation was observed in CA1 (rs = 0.455, p = 0.058). Some of MRI-based or pathology-based parameters in the subfields preliminarily showed relationships with the postsurgical memory changes. In conclusion, automated subfield volumetry for patients with hippocampal sclerosis moderately reflects their subfield atrophy and might be useful to predict the postsurgical change of memory function in these patients.

Drying dissipative structures of lycopodium spore particles in aqueous dispersion.

Drying dissipative structures of aqueous dispersions of lycopodium particles (31 microm in average diameter) from the spores of Lycopodium clavatum were studied as a function of the particle concentrations in the presence and the absence of sodium chloride. The drying patterns formed on a cover glass, a watch glass and a Petri glass dish were observed macroscopically and microscopically. Lycopodium particles were the combination of hemisphere and tetrahedron in their shape and possessed the weakly acidic groups on their surfaces. The vague broad ring structure was observed even for the very large colloidal particles, and their size on a cover glass decreased as particle concentration decreased. Microscopic drying patterns almost disappeared except the short chain-like patterns. These observations support that the convectional contribution on the dissipative drying pattern formation is still effective in the lycopodium suspensions, though the convectional forces in the suspension are very weak compared with the sedimentation forces.

Development of a novel preparation method of recombinant proteoliposomes using baculovirus gene expression systems.

We have developed a novel method for the preparation of 'recombinant proteoliposomes'. Membrane proteins were expressed on budded virus (BV) envelopes using baculovirus gene expression systems, and proteoliposomes were prepared by fusion of these viruses with liposomes. First, plasmid DNA containing the gene for the thyroid-stimulating hormone receptor (TSHR) or the acetylcholine receptor alpha-subunit (AChRalpha) was co-transfected with wild type virus [Autographa californica nuclear polyhedrosis virus (AcNPV)] genomes into insect cells [Spodoptera frugiperda (Sf9)] to obtain recombinant viruses via homologous recombination. The recombinant viruses were again infected into Sf9 cells, and the resulting BVs were shown to express TSHR and AChRalpha. Next, the fusion behaviour of AcNPV-derived BVs and liposomes was examined via a fluorescence assay, and BVs were shown to fuse with phosphatidylserine-containing liposomes below pH 5.0, the pH at which fusion glycoprotein gp64 on the virus envelope becomes active. TSHR- or AChRalpha-expressed BVs were also shown to fuse with liposomes. Finally, TSHR- and AChRalpha-recombinant proteoliposomes were immobilized on enzyme-linked immunosorbent assay plates, and their reactivities were examined via a general immunoassay, which showed that the recombinant proteoliposomes were fully active. These results successfully demonstrate the development of a method based on a baculovirus gene expression system for the preparation of recombinant and functional proteoliposomes.