The mechanism of neuronal dysfunction via tau aggregation in tauopathy patients is controversial. In Alzheimer’s disease (AD), we previously reported mislocalization of the DNA repair nuclear protein BRCA1, its coaggregation with tau, and the possible importance of the subsequent DNA repair dysfunction. However, whether this dysfunction in BRCA1 also occurs in other tauopathies is unknown. The aim of this study was to evaluate whether BRCA1 colocalizes with tau aggregates in the cytoplasm in the brains of the patients with tauopathy. We evaluated four AD, two Pick’s disease (PiD), three progressive supranuclear palsy (PSP), three corticobasal degeneration (CBD), four normal control, and four disease control autopsy brains. Immunohistochemistry was performed using antibodies against BRCA1 and phosphorylated tau (AT8). Colocalization was confirmed by immunofluorescence double staining. Colocalization of BRCA1 with tau aggregates was observed in neurofibrillary tangles and neuropil threads in AD, pick bodies in PiD, and globose neurofibrillary tangles and glial coiled bodies in PSP. However, only partial colocalization was observed in tuft-shaped astrocytes in PSP, and no colocalization was observed in CBD. Mislocalization of BRCA1 was not observed in disease controls. BRCA1 was mislocalized to the cytoplasm and colocalized with tau aggregates in not only AD but also in PiD and PSP. Mislocalization of BRCA1 by tau aggregates may be involved in the pathogenesis of PiD and PSP.

Objective: Gait movies recorded in daily clinical practice are usually not filmed with specific devices, which prevents neurologists benefitting from leveraging gait analysis technologies. Here we propose a novel unsupervised approach to quantifying gait features and to extract cadence from normal and parkinsonian gait movies recorded with a home video camera by applying OpenPose, a deep learning–based 2D-pose estimator that can obtain joint coordinates from pictures or videos recorded with a monocular camera. Methods: Our proposed method consisted of two distinct phases: obtaining sequential gait features from movies by extracting body joint coordinates with OpenPose; and estimating cadence of periodic gait steps from the sequential gait features using the short-time pitch detection approach. Results: The cadence estimation of gait in its coronal plane (frontally viewed gait) as is frequently filmed in the daily clinical setting was successfully conducted in normal gait movies using the short-time autocorrelation function (ST-ACF). In cases of parkinsonian gait with prominent freezing of gait and involuntary oscillations, using ACF-based statistical distance metrics, we quantified the periodicity of each gait sequence; this metric clearly corresponded with the subjects’ baseline disease statuses. Conclusion: The proposed method allows us to analyze gait movies that have been underutilized to date in a completely data-driven manner, and might broaden the range of movies for which gait analyses can be conducted.

Aggregation of α‐synuclein (α‐syn) into amyloid is the pathological hallmark of several neurodegenerative disorders, including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. It is widely accepted that α‐syn aggregation is associated with neurodegeneration, although the mechanisms are not yet fully understood. Therefore, the inhibition of α‐syn aggregation is a potential therapeutic approach against these diseases. This study used the photocatalyst for α‐syn photo‐oxygenation, which selectively adds oxygen atoms to fibrils. Our findings demonstrate that photo‐oxygenation using this photocatalyst successfully inhibits α‐syn aggregation, particularly by reducing its seeding ability. Notably, we also discovered that photo‐oxygenation of the histidine at the 50th residue in α‐syn aggregates is responsible for the inhibitory effect. These findings indicate that photo‐oxygenation of the histidine residue in α‐syn is a potential therapeutic strategy for synucleinopathies.

Desminopathy is a cardiac and skeletal myopathy caused by disease-causing variants in the desmin (DES) gene and represents a subgroup of myofibrillar myopathies, where cytoplasmic desmin-postive immunoreactivity is the pathological hallmark. We herein report a 28-year-old Japanese man who was initially diagnosed with sporadic hypertrophic cardiomyopathy with atrioventricular block at 9 years old and developed weakness in the soft palate and extremities. The myocardial tissue dissected during implantation of the ventricular-assisted device showed a dilated phase of hypertrophic cardiomyopathy and intracellular accumulation of proteinase K-resistant desmin aggregates. Genetic testing confirmed a de novo mutation of DES, which has already been linked to desminopathy. As the molecular diagnosis of desminopathy is challenging, particularly if patients show predominantly cardiac signs and a routine skeletal muscle biopsy is unavailable, these characteristic pathological findings of endomyocardial proteinase K-resistant desmin aggregates might aid in clinical practice.