Medial temporal atrophy predicts the limbic comorbidities in lewy body disease.

Purpose: Although neuropathological comorbidities, including Alzheimer's disease neuropathological change (AD-NC) and limbic-predominant age-related TAR DNA-binding protein 43encephalopathy neuropathological change (LATE-NC), are associated with medial temporal atrophy in patients with Lewy body disease (LBD), the diagnostic performance of magnetic resonance imaging (MRI)-derived indices remains unclear. This study aimed to investigate the diagnostic performance of MRI-derived indices representing medial temporal atrophy in differentiating between LBD with AD-NC and/or LATE-NC (mixed LBD [mLBD]) and without these comorbidities (pure LBD [pLBD]).

Methods: This study included 24 and 16 patients with pathologically confirmed mLBD and pLBD, respectively.

UBL3 Interacts with PolyQ-Expanded Huntingtin Fragments and Modifies Their Intracellular Sorting.

Background/objectives: UBL3 (Ubiquitin-like 3) is a protein that plays a crucial role in post-translational modifications, particularly in regulating protein transport within small extracellular vesicles. While previous research has predominantly focused on its interactions with α-synuclein, this study investigates UBL3's role in Huntington's disease (HD). HD is characterized by movement disorders and cognitive impairments, with its pathogenesis linked to toxic, polyglutamine (polyQ)-expanded mutant huntingtin fragments (mHTT).

A novel tauopathy model mimicking molecular and spatial aspects of human tau pathology.

Creating a mouse model that recapitulates human tau pathology is essential for developing strategies to intervene in tau-induced neurodegeneration. However, mimicking the pathological features seen in human pathology often involves a trade-off with artificial effects such as unexpected gene insertion and neurotoxicity from the expression system. To overcome these issues, we developed the rTKhomo mouse model by combining a transgenic CaMKII-tTA system with a P301L mutated 1N4R human tau knock-in at the locus with a C57BL/6J background.

Voxel-Based Morphometry of Progressive Supranuclear Palsy Using a 3D Fast Low-angle Shot Localizer Image: A Comparison with Magnetization-Prepared Rapid Gradient Echo.

Purpose: Voxel-based morphometry (VBM) is widely used to investigate white matter (WM) atrophy in patients with progressive supranuclear palsy (PSP). In contrast to high-resolution 3D T1-weighted imaging such as magnetization-prepared rapid acquisition with gradient echo (MPRAGE) sequences, the utility of other 3D sequences has not been sufficiently evaluated. This study aimed to assess the feasibility of using a 3D fast low-angle shot sequence captured as a localizer image (L3DFLASH) for VBM analysis of WM atrophy patterns in patients with PSP.

Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

Background: The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs.

The influence of limbic-predominant age-related TDP-43 encephalopathy on argyrophilic grain disease: A voxel-based morphometry analysis of pathologically confirmed cases.

Background: The influence of limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathological change (LATE-NC) on structural alterations in argyrophilic grain disease (AGD) have not been documented. This study aimed to investigate the morphological impact of LATE-NC on AGD through voxel-based morphometry (VBM) technique.

Materials And Methods: Fifteen individuals with pathologically verified AGD, comprising 6 with LATE-NC (comorbid AGD [cAGD]) and 9 without LATE-NC (pure AGD [pAGD]), along with 10 healthy controls (HC) were enrolled.

Voxel-based Morphometry of Alzheimer's Disease Using a Localizer Image: A Comparative Study with Magnetization Prepared Rapid Acquisition with Gradient Echo.

Purpose: Magnetization prepared rapid acquisition with gradient echo (MPRAGE) sequence is a gold-standard technique for voxel-based morphometry (VBM) because of high spatial resolution and excellent tissue contrast, especially between gray matter (GM) and white matter (WM). Despite its benefits, MPRAGE exhibits distinct challenge for VBM in some patients with neurological disease because of long scan time and motion artifacts. Speedily acquired localizer images may alleviate this problem.

Asymmetric Cerebral Peduncle Atrophy: A Simple Diagnostic Clue for Distinguishing Frontotemporal Lobar Degeneration from Alzheimer's Disease.

Background: Due to confusing clinicoradiological features such as amnestic symptoms and hippocampal atrophy in frontotemporal lobar degeneration (FTLD), antemortem differentiation between FTLD and Alzheimer's disease (AD) can be challenging. Although asymmetric atrophy of the cerebral peduncle is regarded as a representative imaging finding in some disorders of the FTLD spectrum, the utility of this finding has not been sufficiently evaluated for differentiating between FTLD and AD.

Objective: This study aimed to explore the diagnostic performance of asymmetric cerebral peduncle atrophy on axial magnetic resonance imaging as a simple radiological discriminator between FTLD and AD.

Lipid-correlated alterations in the transcriptome are enriched in several specific pathways in the postmortem prefrontal cortex of Japanese patients with schizophrenia.

Aims: Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021).

NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment.

The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis.

Voxel-Based and Surface-Based Morphometry Analysis in Patients with Pathologically Confirmed Argyrophilic Grain Disease and Alzheimer's Disease.

Background: Due to clinicoradiological similarities, including amnestic cognitive impairment and limbic atrophy, differentiation of argyrophilic grain disease (AGD) from Alzheimer's disease (AD) is often challenging. Minimally invasive biomarkers, especially magnetic resonance imaging (MRI), are valuable in routine clinical practice. Although it is necessary to explore radiological clues, morphometry analyses using new automated analytical methods, including whole-brain voxel-based morphometry (VBM) and surface-based morphometry (SBM), have not been sufficiently investigated in patients with pathologically confirmed AGD and AD.

Diverse limbic comorbidities cause limbic and temporal atrophy in lewy body disease.

Background: In contrast to Alzheimer's disease (AD)-related pathology, the influence of comorbid limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) or argyrophilic grains (AG) on structural imaging in Lewy body disease (LBD) has seldom been evaluated.

Objective: This study aimed to investigate whether non-AD limbic comorbidities, including LATE-NC and AG, cause cortical atrophy in LBD.

Methods: Seventeen patients with pathologically confirmed LBD with lower Braak neurofibrillary tangle stage ( View Article and Find Full Text PDF

Severe cerebrovascular pathology of the first supercentenarian to be autopsied in the world.

We report on a 116-year-old Japanese woman who was the first officially documented supercentenarian to be autopsied in the world. She lived a remarkably healthy life until suffering cerebral infarction at 109 years of age. She became Japan's oldest person at 113 years and died in 1995 from colon cancer at 116 years 175 days.

Expression of Transferrin Protein and Messenger RNA in Neural Cells from Mouse and Human Brain Tissue.

Iron is an essential nutrient in the body. However, iron generates oxidative stress and hence needs to be bound to carrier proteins such as the glycoprotein transferrin (Tf) in body fluids. We previously reported that cerebrospinal fluid contains Tf glycan-isoforms that are derived from the brain, but their origins at the cellular level in the brain have not yet been elucidated.

A Histochemical Analysis of Neurofibrillary Tangles in Olfactory Epithelium, a Study Based on an Autopsy Case of Juvenile Alzheimer's Disease.

The pathological changes of Alzheimer's disease (AD) begin 10-20 years before clinical onset, and it is therefore desirable to identify effective methods for early diagnosis. The nasal mucosa is a target tissue for measuring AD-related biomarkers because the olfactory nerve is the only cranial nerve that is exposed to the external environment. We describe an autopsy case of rapidly advanced juvenile AD (JAD), focusing on the olfactory system.

Clinicoradiological Features in Progressive Supranuclear Palsy Comorbid with Argyrophilic Grains.

Background: Contrary to pure cases, the influence of comorbid argyrophilic grain disease (AGD) in progressive supranuclear palsy (PSP) has not been sufficiently evaluated.

Objectives: We compared the clinicoradiological features of 12 patients with PSP with (PSPw/AG) and 8 patients without AGD (PSPw/oAG).

Methods: Medical records and magnetic resonance imaging were checked retrospectively from a single brain bank database.

Ultrastructural and biochemical classification of pathogenic tau, α-synuclein and TDP-43.

Intracellular accumulation of abnormal proteins with conformational changes is the defining neuropathological feature of neurodegenerative diseases. The pathogenic proteins that accumulate in patients' brains adopt an amyloid-like fibrous structure and exhibit various ultrastructural features. The biochemical analysis of pathogenic proteins in sarkosyl-insoluble fractions extracted from patients' brains also shows disease-specific features.

Macroscopic findings of brain with dementia.

In this paper, we have described the points to be noted when examining the macroscopic findings of the brain of patients with dementia. The characteristics of the macroscopic findings of the brain of patients with dementia are shown in the figure of the outer surface and the cut surface. Gross findings in the brain of patients with Alzheimer's disease should consider, in addition to the degree of limbic changes, whether the atrophy is diffuse, the degree of ventricular enlargement, and the complications of vascular changes.

Sloping Shoulders Sign: A Practical Radiological Sign for the Differentiation of Alzheimer's Disease and Argyrophilic Grain Disease.

Background: Although hippocampal atrophy is a well-known imaging biomarker of Alzheimer's disease (AD), this finding is not useful to differentiate AD from argyrophilic grain disease (AGD) which is a common AD mimicker presenting with similar amnestic symptoms and medial temporal atrophy. Instead, we propose use of the "sloping shoulders sign", defined as a distinct configuration of the bilateral hippocampal heads showing lateral and downward slopes on axial magnetic resonance imaging (MRI).

Objective: We investigated the diagnostic utility of the "sloping shoulders sign" as a simple radiological discriminator of AD from AGD.