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The hypothalamus is the region of the brain that integrates the neuroendocrine system and whole‐body metabolism. Patients with Alzheimer's disease (AD) have been reported to exhibit pathological changes in the hypothalamus, such as neurofibrillary tangles (NFTs) and amyloid plaques (APs). However, few studies have investigated whether hypothalamic AD pathology is associated with clinical factors. We investigated the association between AD‐related pathological changes in the hypothalamus and clinical pictures using autopsied brain samples obtained from deceased residents of a Japanese community. A total of 85 autopsied brain samples were semi‐quantitatively analyzed for AD pathology, including NFTs and APs. Our histopathological studies showed that several hypothalamic nuclei, such as the tuberomammillary nucleus (TBM) and lateral hypothalamic area (LHA), are vulnerable to AD pathologies. NFTs are observed in various neuropathological states, including normal cognitive cases, whereas APs are predominantly observed in AD. Regarding the association between hypothalamic AD pathologies and clinical factors, the degree of APs in the TBM and LHA was associated with a lower body mass index while alive, after adjusting for sex and age at death. However, we found no significant association between hypothalamic AD pathology and the prevalence of hypertension, diabetes, or dyslipidemia. Our study showed that a lower BMI, which is a poor prognostic factor of AD, might be associated with hypothalamic AP pathology and highlighted new insights regarding the disruption of the brain–whole body axis in AD. [ABSTRACT FROM AUTHOR]

Neuronal intranuclear inclusions (NIIs) are common key structures in polyglutamine (polyQ) diseases such as Huntington disease (HD), spinocerebellar ataxia type 1 (SCA1), and SCA3. Marinesco bodies (MBs) of dopaminergic neurons in the substantia nigra are also intranuclear structures and are frequently seen in normal elderly people. Ribosomal dysfunction is closely related to two differential processes; therefore, we aimed to identify the pathological characteristics of ribosomal protein SA (RPSA), a ribosomal protein, in both states. To this end, we evaluated the autopsy findings in four patients with HD, two SCA3, and five normal elderly cases (NCs). Immunohistochemical studies demonstrated that both NIIs and MBs contain RPSA. In polyQ diseases, RPSA was co‐localized with polyQ aggregations, and 3D‐reconstructed images revealed their mosaic‐like distribution. Assessments of the organization of RPSA and p62 in NIIs showed that RPSA was more localized toward the center than p62 and that this unique organization was more evident in the MBs. Immunoblotting of the temporal cortices revealed that the nuclear fraction of HD patients contained more RPSA than that of NCs. In conclusion, our study revealed that RPSA is a common component of both NIIs and MBs, indicating that a similar mechanism contributes to the formation of polyQ NIIs and MBs. [ABSTRACT FROM AUTHOR]

Here we present the autopsy case of an 80‐year‐old woman with a 9‐year history of motor neuron disease and atypical Parkinsonism. Her initial symptom was gait disturbance, and she subsequently developed limb weakness and Parkinsonism without response to levodopa. Her motor symptoms progressed to bulbar palsy, and she died of respiratory failure. Postmortem examination revealed characteristic findings of amyotrophic lateral sclerosis (ALS), including motor neuronal loss with astrogliosis, corticospinal tract degeneration, and TAR DNA‐binding protein of 43 kDa abnormalities, including nuclear loss and skein‐like inclusions. In contrast, severe tau pathological changes were seen in the frontotemporal lobes and pallido‐nigral system. Tau pathologies affected not only neuronal components, such as neurofibrillary tangles and neuropil threads, but also glial cells (astrocytes and oligodendrocytes). Some glial tau pathologies exhibited peculiar round accumulations, reminiscent of globular glial inclusions (GGIs) in globular glial tauopathy. This unique autopsy case demonstrates that ALS with TDP‐43 could be comorbid with globular glial tau inclusions and indicates that common pathological mechanisms exist among ALS and GGI formation. [ABSTRACT FROM AUTHOR]

Over 60% of all patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been diagnosed in Japan. The incubation period has ranged from 1 to 30 years and the age at onset from 15 to 80 years. Here, we report a 77-year-old male Japanese autopsied dCJD case with the longest incubation period so far in Japan. He received a cadaveric dural graft at the right cranial convexity following a craniotomy for meningioma at the age of 46. At 30 years post-dural graft placement, disorientation was observed as an initial symptom of dCJD. He rapidly began to present with inconsistent speech, cognitive impairment and tremor of the left upper extremity. Occasional myoclonic jerks were predominantly observed on the left side. Brain MRI presented hyperintense signals on diffusion-weighted and T2-weighted images, at the right cerebral cortex. The most hyperintense lesion was located at the right parietal lobe, where the dura mater graft had been transplanted. Single-photon emission CT scan showed markedly decreased cerebral blood flow at the right parietal lobe. EEG revealed diffuse and slow activities with periodic sharp-wave complex discharges seen in the right parietal, temporal and occipital lobes. He died of pneumonia 9 months after onset. Brain pathology revealed non-plaque-type dCJD. Laterality of neuropathological changes, including spongiform change, neuronal loss, gliosis or PrP deposits, was not evident. Western blot analysis showed type 1 PrPCJD. Alzheimer-type pathology and PSP-like pathology were also observed. [ABSTRACT FROM AUTHOR]