Importance of repeated computed tomography on pediatric traumatic acute posterior fossa subdural hematoma: A case study.

Traumatic acute posterior fossa subdural hematoma (PFSDH) is a rare and potentially fatal condition in which the progressed hematoma compresses the brainstem or causes secondary hydrocephalus. Hence, vigilant monitoring of clinical and radiological findings is crucial to detect the typical sudden deterioration, which can occur in the early stages. However, managing pediatric PFSDHs poses additional challenges due to risks associated with radiation exposure from repeat computed tomography (CT) examinations, potentially impeding crucial diagnostic insights. Here, we present a rare pediatric case of fatal acute traumatic PFSDH. Despite undergoing a timely initial CT scan that indicated the presence of PFSDH, the patient experienced sudden deterioration 15 h later and eventually died. No follow-up CT examinations were conducted during this critical period. This case underscores the challenges in managing pediatric PFSDHs, particularly concerning the benefits of repeated CT examinations in initially stable patients.

ASK1 activation in glial cells in post-mortem multiple sclerosis tissue.

Multiple sclerosis (MS), the leading cause of disability in young adults, is an inflammatory disease of the central nervous system characterized by localized areas of demyelination. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been shown to be implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Interestingly, ASK1 signaling regulates glial cell interactions and drives neuroinflammation in EAE mice. To further investigate its clinical significance, in the present study, we examined the activation of ASK1 in the post-mortem brain of MS patients. ASK1 activation was found in active lesions of the corpus callosum in both microglia/macrophages and astrocytes. Moreover, ASK1 activation in astrocytes was higher than that in microglia/macrophages, which was in line with our findings in EAE mice. Our results suggest an important role of ASK1 in glial cells, indicating that ASK1 might be a good therapeutic target for MS.

Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome.

The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration was diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%) and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. In addition, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group [P = 0.005, odds ratio (95% confidence interval): 31.67 (1.46-685.34)]. Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome [P = 0.047, 6.75 (1.16-39.20)]. Pyramidal sign at presentation and personality change during the entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome [P = 0.011, 27.44 (1.25-601.61), and P = 0.013, 40.00 (1.98-807.14), respectively]. In corticobasal syndrome, decision tree analysis revealed that 'freezing at onset' or 'no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset' predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. 'Dysarthria at presentation and age at onset over 61 years' suggested progressive supranuclear palsy pathology, and 'pyramidal sign at presentation and personality change during the entire course' implied Alzheimer's disease pathology. In conclusion, frozen gait at onset, dysarthria, personality change and pyramidal signs may be useful clinical signs for predicting background pathologies in corticobasal syndrome.

Two medicolegal autopsy cases of multinodular and vacuolating neuronal tumor revealed by postmortem MRI.

The multinodular and vacuolating neuronal tumor (MVNT) is a recently recognized brain lesion. MVNT has a characteristic appearance in MRI images and is potentially epileptogenic. To the best of our knowledge, no report has yet described this pathological entity in the forensic medicine literature. We present two medicolegal autopsy cases where postmortem MRI (PMMR) was useful to detect this lesion. Case 1: a man in his 30s, with about a 7-year history of intractable epilepsy and known MVNT died suddenly. Although MVNT was not detected in the initial morphological evaluation during autopsy, PMMR of the formalin-fixed brain revealed the lesion in the left frontal lobe. Histopathology confirmed it as a MVNT. Case 2: a man in his 20s hanged himself to death. PMMR prior to autopsy revealed MVNT in his brain, and the diagnosis was confirmed by a detailed histopathological evaluation. In both cases, postmortem CT was not useful for evaluation. The cases suggested that MVNT can cause sudden, unexpected epileptic death, and pre- or post-autopsy PMMR may be useful to detect it.

Case report: Fatal ischemic stroke induced by unruptured traumatic intracranial vertebral artery dissection.

Intracranial vertebral artery dissection (IVAD) is rare and potentially fatal due to the risk of secondary subarachnoid hemorrhage once ruptured. Unruptured traumatic IVAD is even rarer and can result in ischemic stroke, yet mostly benign when timely diagnosed. Herein, we present an uncommon case of a patient who underwent a fatal ischemic stroke induced by unruptured traumatic IVAD. The patient was symptomatic soon after being physically assaulted but left untreated until acute deterioration for multiple brain infarctions occurred, secondary to IVAD-induced cerebellar stroke. Fifteen days later, he died, regardless of an urgently performed thrombectomy. Multiple serial histologic examinations revealed an unruptured dissection of the intracranial vertebral artery with a slit-like tear of the intimal and medial layers, considered to be the culprit lesion. The 15-day prolonged onset of stroke was rare in traumatic IVADs. Furthermore, the slit-like tear of the intimal layer in our case may support the initial intimal laceration hypothesis for VAD pathogenesis. Since limited pathohistological information is available regarding ischemic IVAD, we believe this rare case will be beneficial in understanding the pathophysiology of ischemic IVAD.

PLA2G2E-mediated lipid metabolism triggers brain-autonomous neural repair after ischemic stroke.

The brain is generally resistant to regeneration after damage. The cerebral endogenous mechanisms triggering brain self-recovery have remained unclarified to date. We here discovered that the secreted phospholipase PLA2G2E from peri-infarct neurons generated dihomo-γ-linolenic acid (DGLA) as necessary for triggering brain-autonomous neural repair after ischemic brain injury. Pla2g2e deficiency diminished the expression of peptidyl arginine deiminase 4 (Padi4), a global transcriptional regulator in peri-infarct neurons. Single-cell RNA sequencing (scRNA-seq) and epigenetic analysis demonstrated that neuronal PADI4 had the potential for the transcriptional activation of genes associated with recovery processes after ischemic stroke through histone citrullination. Among various DGLA metabolites, we identified 15-hydroxy-eicosatrienoic acid (15-HETrE) as the cerebral metabolite that induced PADI4 in peri-infarct-surviving neurons. Administration of 15-HETrE enhanced functional recovery after ischemic stroke. Thus, our research clarifies the promising potential of brain-autonomous neural repair triggered by the specialized lipids that initiate self-recovery processes after brain injury.

Disease specific brain capillary angiopathy in schizophrenia, bipolar disorder, and Alzheimer's disease.

Schizophrenia (SZ) and bipolar disorder (BD), which are both psychiatric disorders, share some common clinical evidence. We recently discovered that brain capillary angiopathy is another common feature of these psychiatric disorders using fibrin accumulation in vascular endothelial cells as an indicator. This study aimed to characterize the similarities and differences in cerebral capillary injuries in various brain diseases to provide new diagnostic methods for SZ and BD and to develop new therapeutic strategies. We evaluated whether discrepancies exist in the degree of vascular damage among SZ and BD and other brain disorders (amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD)) using postmortem brains. Our results demonstrate that fibrin was strongly accumulated in the capillaries of the grey matter (GM) of brains of patients with SZ and AD and in the capillaries of the white matter (WM) in those of patients with SZ, BD, and AD when compared with control subjects without any psychiatric or neurological disease history. However, ALS and PD brains did not present a significant increase in the amount of accumulated fibrin, either in the capillaries of WM or GM. Furthermore, significant leakage of fibrin into the brain parenchyma, indicating a vascular physical disruption, was observed in the brains of patients with AD but not in the brains of other patients compared with control subjects. In conclusion, our work reveals that Fibrin-accumulation in the brain capillaries are observed in psychiatric disorders, such as SZ, BD, and AD. Furthermore, fibrin-accumulating, nonbreaking type angiopathy is characteristic of SZ and BD, even though there are regional differences between these diseases.

Expanded ischemic lesion due to herniation leads to axonal injury in a site remote to the primary lesion on autopsy brain with acute focal cerebral ischemia.

Cerebral ischemia may lead to axonal injury not only at the site of the primary lesion but also in a region remote to the site of insult. In this study, we investigated the effect of herniation on the development of axonal injury at a site remote to the primary lesion during the acute phase of cerebral ischemia. We obtained postmortem brains of 13 cases with acute phase of unilateral cerebral infarction in the territory of the internal carotid artery or middle cerebral artery and seven controls. We classified the brain tissues into herniation and non-herniation groups. Then we examined whether axonal and ischemic changes existed in the corpus callosum contralateral to the ischemic hemisphere and the upper pons. In the herniation group, we detected white-matter lesions by Klüver-Barrera staining, microglial loss by immunohistochemistry for ionized calcium-binding adaptor molecule 1, and axonal injury by immunohistochemistry for amyloid precursor protein. However, none of the aforementioned findings were observed in the non-herniation group. These findings suggest the existence of regional overlap in axonal and ischemic pathologies in remote regions in the presence of herniation. We concluded that herniation may play a significant role in the development of axonal and ischemic changes in the remote region. Our results suggest that axonal injury in a remote region may result from expanded ischemic lesions due to herniation.

An autopsy case report of adult-onset Krabbe disease: Comparison with an infantile-onset case.

Krabbe disease is a lysosomal storage disease caused by a deficiency of the galactocerebrosidase (GALC) enzyme, which leads to demyelination of the central and peripheral nervous systems. Almost all patients with Krabbe disease are infants, and this is the first report of adult-onset cases that describe pathological findings. Here, we present two autopsy cases: a 73-year-old female and a 2-year-old male. The adult-onset case developed symptoms in her late thirties and was diagnosed by the identification of GALC D528N and L634S mutations and by T2-weighted magnetic resonance imaging; she had increased signal in the white matter along the pyramidal tract to the bilateral precentral gyrus, as well as from the triangular part to the posterior horn of the lateral ventricle. Microscopically, Klüver-Barrera staining was pale in the white matter of the precentral gyrus and occipito-thalamic radiation, and a few globoid cells were observed. The GALC mutations that were identified in the present adult-onset case do not completely inactivate GALC enzyme activity, resulting in focal demyelination of the brain.

Distribution of amyloid-ß precursor protein-immunoreactive axons differs according to the severity of cerebral ischemia in autopsy brains.

Amyloid-ß precursor protein (APP) immunohistochemistry has been used to detect axonal injury in forensic neuropathology. However, axonal injury caused by cerebral ischemia has not been investigated by APP immunohistochemistry in detail. In particular, it is unknown if there is a correlation between the prognosis of cerebral ischemia and the distribution of axonal injury detected by APP immunohistochemistry. To address this issue, we compared the distribution of APP-immunoreactive axons in autopsy brains including lesions of acute phase of cerebral infarction in the territory of the middle cerebral artery (MCA) or internal carotid artery (ICA) with the degree of severity. The presence or absence of a midline shift was used as an indicator of the severity of cerebral ischemia. We identified a difference in the distribution of APP-immunoreactive axons between cases with and without a midline shift. In both the groups, APP-immunoreactive axons were detected at the margin of the ischemic lesions; however, only in cases with a midline shift, intense APP-immunoreactive axons were also found in areas other than the MCA and ICA territories, including the white matter of the cerebral hemispheres ipsilateral and contralateral to the ischemic lesions. This distribution was different from that of acute global cerebral ischemia cases reported previously. Our results indicate that the distribution of APP-immunoreactive axons differs according to the severity and type of cerebral ischemia, suggesting that the distribution of APP-immunoreactive axons is associated with the prognosis of cerebral ischemia.

ASK1 signaling regulates phase-specific glial interactions during neuroinflammation.

Neuroinflammation is well known to be associated with neurodegenerative diseases. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that has been implicated in neuroinflammation, but its precise cellular and molecular mechanisms remain unknown. In this study, we generated conditional knockout (CKO) mice that lack ASK1 in T cells, dendritic cells, microglia/macrophages, microglia, or astrocytes, to assess the roles of ASK1 during experimental autoimmune encephalomyelitis (EAE). We found that neuroinflammation was reduced in both the early and later stages of EAE in microglia/macrophage-specific ASK1 knockout mice, whereas only the later-stage neuroinflammation was ameliorated in astrocyte-specific ASK1 knockout mice. ASK1 deficiency in T cells and dendritic cells had no significant effects on EAE severity. Further, we found that ASK1 in microglia/macrophages induces a proinflammatory environment, which subsequently activates astrocytes to exacerbate neuroinflammation. Microglia-specific ASK1 deletion was achieved using a CX3CR1CreER system, and we found that ASK1 signaling in microglia played a major role in generating and maintaining disease. Activated astrocytes produce key inflammatory mediators, including CCL2, that further activated and recruited microglia/macrophages, in an astrocytic ASK1-dependent manner. Astrocyte-specific analysis revealed CCL2 expression was higher in the later stage compared with the early stage, suggesting a greater proinflammatory role of astrocytes in the later stage. Our findings demonstrate cell-type-specific roles of ASK1 and suggest phase-specific ASK1-dependent glial cell interactions in EAE pathophysiology. We propose glial ASK1 as a promising therapeutic target for reducing neuroinflammation.

[Practical Anatomy of the Basal Ganglia].

Anatomical knowledge of target structures is essential in stereotactic functional neurosurgery. Thus, we created a three-dimensional(3D)atlas comprising frozen sections and histologically stained slides prepared from cadaveric brains. Herein, we describe the anatomical information of stereotactic functional neurosurgery targets gained from our atlas. The subthalamic nucleus(STN)was found to be clearly enclosed by neural fibers with high neuronal density. Based on our 3D models, the mean penetration length of deep brain stimulation leading into the STN was 6.6 mm. The globus pallidus was found to be clearly divided into the grobus pallidus externus(GPe)and internus(GPi)by its neural fibers, and the optic tract was located below the GPi. Although the thalamic lateral nuclear group(ventrooralis, ventrontermedius, and ventrocaudalis)could not be identified from either macroscopic frozen sections or MR images, these structures were clearly discernible from each other based on cell architecture(cell size and cell density)when viewed under a microscope. In contrast, distinguishing ventral and dorsal nuclei in humans is difficult. In addition to the main targets of the basal ganglia, we also investigated the anatomy of other targets in detail(posterior subthalamic area, pedunclopontine nucleus, nucleus accumbens, and nucleus basalis of Meynert). Overall, this anatomical knowledge from the atlas helps functional neurosurgeons interpret intraoperative microelectrode recording and MRI more precisely, helping facilitate more accurate surgeries.

Fatal intracranial hemorrhage due to infantile acute lymphoblastic leukemia mimicking abusive head trauma.

We report the case of a 2-month-old infant who was found moribund in her crib. Postmortem computed tomography (PMCT) was performed before autopsy. As the baby had a severe subdural hematoma, retinal hemorrhage, and encephalopathy on PMCT, abusive head trauma (AHT) was tentatively diagnosed. At autopsy, no scalp hemorrhages or skull fractures were found; however, the classic triad of AHT was present, mainly on the right side. Additionally, there was dark red discoloration around the heart, and the liver, spleen, and pancreas were enlarged. Peripheral blood was macroscopically cloudy with marked leukocytosis. After careful histological examination, B-cell precursor acute lymphoblastic leukemia (ALL) was diagnosed. All the macroscopic lesions could be attributed to ALL. The manner of death was natural. To the best of our knowledge, this is the first report of infantile ALL mimicking AHT on PMCT images. This case demonstrates the importance of a comprehensive systematic approach to considering differential diagnosis when PMCT shows multiple intracranial hemorrhages suggestive of AHT in an infant.

Inappropriate diet and fatal malnutrition in a 10-year-old child fed only infant formula throughout life: Novel pathological diagnostic criterion for starvation via lipophagy.

Fatal starvation is rarely seen in developed countries; when it occurs, it may be associated with medicolegal problems. Forensic pathologists are required to determine leading causes of death and provide opinions on the influence of starvation, especially in cases of suspected child abuse. Recently, starvation-induced steatosis was suggested to be regulated by lipophagy. Here, we report an extremely rare case of death by malnutrition of a 10-year-old boy, who was fed only infant formula throughout his life. The deceased presented with severe hepatic steatosis, probably related to prolonged malnutrition. Fatty liver changes, with deposition of small lipid droplets deposited in the peripheral lobules. High levels of P62 protein (overexpression of which indicates an autophagy impairment) were seen around the central vein region, whereas light-chain-3 (LC3) protein (an indicator of lipophagy activation) was unremarkable. Thus, in our case, impaired lipophagy influenced starvation-induced steatosis. To our knowledge, this article is the first to evaluate the application of lipophagy in forensic investigations as an objective diagnostic criterion.

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies.

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

mTORC2 links growth factor signaling with epigenetic regulation of iron metabolism in glioblastoma.

In cancer, aberrant growth factor receptor signaling reprograms cellular metabolism and global gene transcription to drive aggressive growth, but the underlying mechanisms are not well-understood. Here we show that in the highly lethal brain tumor glioblastoma (GBM), mTOR complex 2 (mTORC2), a critical core component of the growth factor signaling system, couples acetyl-CoA production with nuclear translocation of histone-modifying enzymes including pyruvate dehydrogenase and class IIa histone deacetylases to globally alter histone acetylation. Integrated analyses in orthotopic mouse models and in clinical GBM samples reveal that mTORC2 controls iron metabolisms via histone H3 acetylation of the iron-related gene promoter, promoting tumor cell survival. These results nominate mTORC2 as a critical epigenetic regulator of iron metabolism in cancer.

DOCK8 is expressed in microglia, and it regulates microglial activity during neurodegeneration in murine disease models.

Dedicator of cytokinesis 8 (DOCK8) is a guanine nucleotide exchange factor whose loss of function results in immunodeficiency, but its role in the central nervous system (CNS) has been unclear. Microglia are the resident immune cells of the CNS and are implicated in the pathogenesis of various neurodegenerative diseases, including multiple sclerosis (MS) and glaucoma, which affects the visual system. However, the exact roles of microglia in these diseases remain unknown. Herein, we report that DOCK8 is expressed in microglia but not in neurons or astrocytes and that its expression is increased during neuroinflammation. To define the role of DOCK8 in microglial activity, we focused on the retina, a tissue devoid of infiltrating T cells. The retina is divided into distinct layers, and in a disease model of MS/optic neuritis, DOCK8-deficient mice exhibited a clear reduction in microglial migration through these layers. Moreover, neuroinflammation severity, indicated by clinical scores, visual function, and retinal ganglion cell (RGC) death, was reduced in the DOCK8-deficient mice. Furthermore, using a glaucoma disease model, we observed impaired microglial phagocytosis of RGCs in DOCK8-deficient mice. Our data demonstrate that DOCK8 is expressed in microglia and regulates microglial activity in disease states. These findings contribute to a better understanding of the molecular pathways involved in microglial activation and implicate a role of DOCK8 in several neurological diseases.

Autopsy report of a late delayed radiation injury after a period of 45 years.

For delayed radiation injury, image analysis has considerably advanced, but neuropathological findings are still required to establish diagnosis. A patient who had received radiation therapy for pineal germinoma at age 14 developed neurological and psychiatric abnormalities after 15 years as a late delayed radiation injury. Autopsy at age 59 revealed diffuse changes in the white matter consisting in order of severity of myelin pallor, demyelination, and necrosis which were characterized by a lack of glial reaction. The cerebral cortex was relatively well preserved. As delayed radiation injuries, hyalinous changes in the vascular wall, angiomatous lesions and, fresh and old petechial hemorrhages were found. Moreover, vascular changes associated with arteriosclerosis were also present. Furthermore, a focal glial nodule was detected which was considered to be a new radiation-induced neoplasia. These findings suggest that late delayed radiation injury may slowly develop over 30 years and may involve damage to neuroglial stem cell compensation. It is also evident that arteriosclerotic changes and newly induced neoplasia may develop in delayed radiation injury cases.

Traumatic axonal injury revealed by postmortem magnetic resonance imaging: A case report.

In forensic investigations, it is important to detect traumatic axonal injuries (TAIs) to reveal head trauma that might otherwise remain occult. These lesions are subtle and frequently ambiguous on macroscopic evaluations. We present a case of TAI revealed by pre-autopsy postmortem magnetic resonance imaging (PMMR). A man in his sixties was rendered unconscious in a motor vehicle accident. CT scans revealed traumatic mild subarachnoid hemorrhage. Two weeks after the accident he regained consciousness, but displayed an altered mental state. Seven weeks after the accident, he suddenly died in hospital. Postmortem computed tomography (PMCT) and PMMR were followed by a forensic autopsy. PMMR showed low-intensity lesions in parasagittal white matter, deep white matter, and corpus callosum on three-dimensional gradient-echo T1-weighted imaging (3D-GRE T1WI). In some of these lesions, T2∗-weighted imaging also showed low-intensity foci suggesting hemorrhagic axonal injury. The lesions were difficult to find on PMCT and macroscopic evaluation, but were visible on antemortem MRI and confirmed as TAIs on histopathology. From this case, it can be said that PMMR can detect subtle TAIs missed by PMCT and macroscopic evaluation. Hence, pre-autopsy PMMR scanning could be useful for identifying TAIs during forensic investigations.

Immunoreactivity of a G protein-coupled l-DOPA receptor GPR143, in Lewy bodies.

l-3,4-Dihydroxyphenylalanine (l-DOPA) has been believed to be an inert amino acid precursor of dopamine, and is the most effective therapeutic agent in Parkinson's disease (PD). We proposed l-DOPA as a neurotransmitter in the central nervous system. Recently, the ocular albinism 1 gene product, OA1/GPR143 (GPR143), was identified as a receptor for l-DOPA. In this study, we examined by generating anti-human GPR143 antibody, the localization of GPR143-immunoreactive signals in the brains from control and PD subjects. GPR143-immunoreactive signals were detected throughout the entire midbrain including substantia nigra pars compacta. In the PD brains, we found that GPR143-immunoreactive signals were detected in Lewy bodies and were colocalized with immunoreactive signals with anti-human Ser129 phosphorylated α-synuclein antibody. Although the significance of its occurrence in the inclusion bodies is unknown, our finding suggests possible implications of GPR143 in PD.