Biomarker-related phospho-tau217 appears in synapses around Aβ plaques prior to tau tangle in cerebral cortex of preclinical Alzheimer's disease.

Phospho-tau protein p-tau181 is a cerebrospinal fluid biomarker for Alzheimer's disease (AD), while p-tau217 is the most sensitive plasma biomarker for cerebral amyloid β (Aβ) load prior to tau pathology in preclinical AD. Diagnostic and prognostic use of these p-tau biomarkers requires neuropathological interpretation. Here, we analyzed the cellular localization of biomarker p-tau species in postmortem human brains harboring different extents of Aβ plaque and tau pathology.

HAPLN2 forms aggregates and promotes microglial inflammation during brain aging in mice.

Protein aggregation is a hallmark of neurodegenerative diseases and is also observed in the brains of elderly individuals without such conditions, suggesting that aging drives the accumulation of protein aggregates. However, the comprehensive understanding of age-dependent protein aggregates involved in brain aging remains unclear. Here, we investigated proteins that become sarkosyl-insoluble with age and identified hyaluronan and proteoglycan link protein 2 (HAPLN2), a hyaluronic acid-binding protein of the extracellular matrix at the nodes of Ranvier, as an age-dependent aggregating protein in mouse brains.

Contemporary positive signs of functional limb weakness in post-acute sequelae of SARS-CoV-2: an exploratory analysis of their utility in diagnosis and follow-up.

Background: Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND.

Visual hallucinations in Parkinson's disease: The critical role of intermediate nucleus basalis of Meynert.

Background And Objective: Patients with Parkinson's disease (PD) often experience visual hallucinations (VH) and delusions. PD patients with VH reportedly have a higher incidence of dementia than PD patients without VH. The nucleus basalis of Meynert (nbM) comprises acetylcholine-releasing neurons that are critical for memory, attention, and arousal.

Diverse tau pathologies in late-life mood disorders revealed by PET and autopsy assays.

Introduction: Late-life mood disorders (LLMDs) may represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer's disease (AD) and non-AD tau pathologies in LLMD participants.

Methods: Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using F-florzolotau and C-Pittsburgh compound B.

Association of rare missense variants with Alzheimer's disease in the Japanese population.

BackgroundLittle is known about the rare missense variants (RMVs) of in East Asians, including the Japanese, and their association with Alzheimer's disease (AD) and lipid metabolism.ObjectiveTo identify RMVs in the Japanese population and investigate their association with AD and lipid metabolism, including low-density lipoprotein cholesterol levels.Methods RMVs were explored in the Niigata (NIG; 2589 subjects) and Tohoku (ToMMo; 3307 subjects) cohorts.

Two Brothers With ADSS1 Myopathy: A Report of Clinical, Radiological, and Autopsy Findings.

ADSS1 myopathy, previously known as adenylosuccinate synthetase-like 1 (ADSSL1) myopathy, is an autosomal recessive muscle disease caused by variants in ADSS1 (adenylosuccinate synthase 1). ADSS1 myopathy is complicated by respiratory muscle weakness or cardiomyopathy as well as limb muscle weakness. We analyzed two siblings with ADSS1 myopathy, both harboring compound heterozygous pathogenic variants (c.

Long-standing preservation of levodopa response in progressive supranuclear palsy.

The clinical and neuropathological characteristics of progressive supranuclear palsy (PSP) with preservation of levodopa (L-dopa) response are described in this report. We present the case of a 73-year-old Japanese man with a 13-year history of dopa-responsive Parkinsonism and abnormalities observed in metaiodobenzylguanidine (MIBG) myocardial scintigraphy, suggesting Parkinson's disease. However, autopsy results revealed PSP pathology, including tuft-shaped astrocytes and globose-type neurofibrillary tangles, without Lewy body pathology.

Post-acute sequelae of SARS-CoV-2 mimic: An important neurological condition.

Background And Objectives: In 2024, the sequalae of the acute phase of coronavirus disease-19 (COVID-19) infection, which include neurological symptoms and are commonly referred to as long COVID or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PASC), continue to be a substantial health concern; however, similar symptoms are observed in individuals with no previous COVID-19 infection.

Methods: This was a single-center, retrospective, descriptive case series study. Data were obtained from patients who visited our outpatient clinic specializing in PASC between June 1, 2021, and May 31, 2023.

Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors.

Introduction: Low-grade epilepsy-associated tumors are the second most common histopathological diagnoses in cases of drug-resistant focal epilepsy. However, the connection between neuroimaging features and genetic alterations in these tumors is unclear, prompting an investigation into genotype-relevant neuroimaging characteristics.

Methods: This study retrospectively analyzed neuroimaging and surgical specimens from 46 epilepsy patients with low-grade epilepsy-associated neuroepithelial tumors that had genetic mutations identified through panel sequencing to investigate their relationship to genotypes.

Clinical characteristics of motor functional neurological disorder manifesting as limb weakness after vaccination against coronavirus disease 2019: A case series.

Background: The characteristics of functional limb weakness (FLW) as one of the manifestations of functional neurological disorder after vaccination against coronavirus disease 2019 (COVID-19) remain controversial.

Methods: In this descriptive case series, we aimed to elucidate the characteristics of Japanese patients with FLW who claimed muscle weakness after COVID-19 vaccination among patients who visited our outpatient clinic between 1 June 2021 and 31 December 2022.

Results: Nine patients were diagnosed with FLW (mean age: 30.

Functional Neurological Disorder Overlapping Paroxysmal Kinesigenic Dyskinesia Confirmed by Genetic Diagnosis.

Functional neurological disorder (FND) may mimic various kinds of neurologic diseases and may coexist with other neurologic disorders. In cases overlapped by FND, it might be challenging to distinguish symptoms induced by FND and those induced by other underlying neurological disorders, especially when patients show no positive signs indicative of FND. Here, we present the case of a patient who was genetically diagnosed with paroxysmal kinesigenic dyskinesia (PKD).

Distinctive chaperonopathy in skeletal muscle associated with the dominant variant in DNAJB4.

DnaJ homolog, subfamily B, member 4, a member of the heat shock protein 40 chaperones encoded by DNAJB4, is highly expressed in myofibers. We identified a heterozygous c.270 T > A (p.

Clinical features of patients who visited the outpatient clinic for long COVID in Japan.

Background: The clinical course, comorbidity, and management of symptoms after the acute phase of coronavirus disease 2019 (COVID-19) remain controversial.

Methods: This was a descriptive case series study, examining the characteristics of patients with longstanding symptoms related to COVID-19 who visited our outpatient clinic between 1 June and 31 December 2021. We analyzed patients' background, chief complaints, clinical course after COVID-19 onset, and clinical examination results.

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.

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.

Unique Lewy pathology in myotonic dystrophy type 1.

Lewy body-related α-synucleinopathy (Lewy pathology) has been reported in patients with myotonic dystrophy (DM) type 1 (DM1), but no detailed report has described the prevalence and extent of its occurrence. We studied consecutive full autopsy cases of DM1 at the National Center of Neurology and Psychiatry (NCNP) Brain Bank for intractable psychiatric and neurological disorders. Thirty-two cases, genetically determined to be DM1 (59.

Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy.

Aims: Oculopharyngodistal myopathy (OPDM) is caused by the expansion of CGG repeats in NOTCH2NLC (OPDM_NOTCH2NLC) GIPC1 (OPDM_GIPC1), or LRP12 (OPDM_LRP12). Neuronal intranuclear inclusion disease (NIID) is clinically distinct from OPDM but is also caused by the expansion of CGG repeats in NOTCH2NLC, which may be an indicator of intranuclear inclusion in skin biopsy. We investigated the presence of intranuclear inclusions in skin biopsies from patients with OPDM and muscle diseases with a similar pathology to evaluate whether they will have similar diagnostic findings on skin biopsy.

Pathology-associated change in levels and localization of SIDT2 in postmortem brains of Parkinson's disease and dementia with Lewy bodies patients.

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are major neurodegenerative disorders that share commonalities in their pathology involving the formation of Lewy bodies, the main component of which is α-synuclein protein. Aberrancy and dysfunction in lysosomes have been suggested to play critical roles in the pathogenesis of Lewy body diseases. We recently identified a novel lysosomal degradation pathway in which various macromolecules, including α-synuclein protein, are directly imported into lysosomes and degraded.