Basic Science and Pathogenesis.

Background: In aging societies, neurodegenerative diseases, such as Alzheimer's disease, are receiving attention. These diseases are primary targets for preemptive medicine, emphasizing the importance of early detection and preventive treatment before the onset of severe, treatment-resistant damages. However, there is a lack of comprehensive investigation of lesions and molecular targets in the entire organ, whereas spatial identification of early-stage lesions is potentially overlooked at the single-cell level.

MYO18B promotes lysosomal exocytosis by facilitating focal adhesion maturation.

Many cancer cells exhibit increased amounts of paucimannose glycans, which are truncated N-glycan structures rarely found in mammals. Paucimannosidic proteins are proposedly generated within lysosomes and exposed on the cell surface through a yet uncertain mechanism. In this study, we revealed that paucimannosidic proteins are produced by lysosomal glycosidases and secreted via lysosomal exocytosis.

Isolation of the feline herpesvirus-1 modified live vaccine strain F2 from one of four cats with dendritic ulcers.

Objectives: To investigate the pathogenicity of feline herpesvirus-1 (FHV-1) to the cornea, FHV-1 strains isolated from feline eyes with dendritic ulcers were subjected to genomic analysis to determine whether FHV-1 vaccine strains are involved in the formation of dendritic ulcers.

Methods: All open reading frame (ORF) sequences of the three F2 strains (Virbac, Intervet and Merial) and the FHV-1 clinical isolates from cats registered in GenBank were compared to detect nucleotide variants unique to the F2 strains, with those nucleotides then being used for simple genotyping of the F2 strains. In all isolates from feline eyes with dendritic ulcers, the regions including nucleotide variants of the F2 strain were amplified with PCR and sequenced.

Phase Control in Monometallic and Alloy Nanomaterials.

Metal nanomaterials with unconventional phases have been recently developed with a variety of methods and exhibit novel and attractive properties such as high activities for various catalytic reactions and magnetic properties. In this review, we discuss the progress and the trends in strategies for synthesis, crystal structure, and properties of phase-controlled metal nanomaterials in terms of elements and the combination of alloys. We begin with a brief introduction of the anomalous phase behavior derived from the nanosize effect and general crystal structures observed in metal nanomaterials.

Basic Science and Pathogenesis.

Background: A polygenic risk score (PRS) estimates an individual's genetic liability for diseases based on accumulated genetic variations. While the PRS has been shown to contribute to the prediction of dementia risk, its utility in predicting the effectiveness of multifactorial interventions to reduce the risk of dementia remains unclear.

Methods: A genome-wide association study (GWAS) was conducted to identify dementia-related traits in the Japanese population.

Basic Science and Pathogenesis.

Background: Previously, we found that germline C3 deletion protected cognition and hippocampal synapses in aged APP/PS1dE9 mice, despite increasing Aß plaques. Here, we crossed our C3 inducible conditional mouse model to APP knockin mice to determine whether global C3 lowering in an adult amyloid mouse model would be protective.

Methods: C3;Rosa26-Cre-ERT2 (C3iKO) mice were crossed to C3;APP mice to generate APP;C3iKO mice, which received 75 mg/kg tamoxifen (TAM; n = 16) or corn oil (CO; n = 15) for 5 days at 3.

Basic Science and Pathogenesis.

Background: Dementia is age-related with a significant genetic contribution, yet genome-wide association studies have not fully accounted for heritability. This discrepancy may in part be due to reliance on SNPs and small indels. Whole-genome sequencing (WGS) data in the Japanese population may reveal population-specific susceptibility loci for dementia.

Basic Science and Pathogenesis.

Background: Mounting evidence support the involvement of adaptive immune system in the pathogenesis of Alzheimer's disease (AD). The current study investigated the age-dependent changes in the abundance of B and T cell subtypes in APP/PS1 mice, a commonly used model for AD.

Method: Peripheral blood was collected through cardiac puncture from 6-, 9-, 12-month-old APP/PS1 transgenic (TG) mice (APPsw and PSEN1dE9, n = 8-12) and their wildtype (WT) littermates (C57BL/6J, n = 12-15).

Basic Science and Pathogenesis.

Background: Continuous speech analysis is considered as an efficient and convenient approach for early detection of Alzheimer's Disease (AD). However, the traditional approach generally requires human transcribers to transcribe audio data accurately. This study applied automatic speech recognition (ASR) in conjunction with natural language processing (NLP) techniques to automatically extract linguistic features from Chinese speech data.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease and a leading cause of senile dementia. Accumulation of amyloid-β (Aβ) in the brains causes chronic neuroinflammation, synaptic loss, and neurovascular damage, which is thought to initiate decades-long AD pathogenesis. Recent clinical trials for anti-Aβ immunotherapy highlights the utility of biomarkers that faithfully reflect Aβ-related brain pathology to diagnose AD at the preclinical stage, to predict the onset and progression of the disease, and to assess the therapeutic efficacy of drugs.

Basic Science and Pathogenesis.

Background: Apolipoprotein E (APOE) ε4 is a significant genetic risk factor for late-onset Alzheimer's Disease and appears to be closely related with brain amyloidosis. Current identification methods for APOE ε4 carriers are mostly based on genotyping which cannot always predict the specific ApoE protein isoform. We present a case study of a sample with a discordant result for genotype compared to the protein isoform (proteotype) and we reflect on possible implications for future applications.

Basic Science and Pathogenesis.

Background: APOE is well recognized to be the most influential susceptibility gene for Alzheimer's disease (AD). For the wild-type allele, e3, it is known that the e4 allele is a risk for AD, while the e2 allele is protective. Recently, genetic analyses with Caucasians have reported the critical associations between APOE rare missense variants (RMVs) and AD, and their importance has been pointed out in terms of disease pathogenesis of AD.

Basic Science and Pathogenesis.

Background: Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia in older people. The clinical feature of DLB includes cognitive impairment, visual hallucinations, parkinsonism, and fluctuating attention. Three genes, SNCA (-synuclein), APOE (apolipoprotein E), and GBA (glucosylceramidase), have been convincingly demonstrated to be associated with DLB.

Basic Science and Pathogenesis.

Background: Alzheimer's Disease (AD) manifests early in the olfactory system, yet its precise role in the pathophysiology of AD remains elusive. This study aims to elucidate the progression of olfactory dysfunction in AD by investigating the dysregulation of the adenosine 2A receptor (A2AR) and its potential involvement in the formation of abnormal plaques and tangles. A2AR plays a pivotal role in modulating synaptic transmission and neuroinflammation by regulating both neurons and glial cells.

Basic Science and Pathogenesis.

Background: Neural circuit hyperexcitability and impaired excitation-to-inhibition (E/I) activity is believed to be a key contributor to synaptic and network degeneration in Alzheimer's disease (AD). Extensive preclinical research on transgenic animal models of AD have demonstrated neuronal and circuit level E/I imbalance mediated by amyloid-beta (Aβ) and tau proteins. Synaptic and network deficits are also integral changes of aging.

Basic Science and Pathogenesis.

Background: Recent genome-wide association analysis has identified Bridging Integrator 1 (BIN1) as one of the genetic risk factors for late-onset AD. In AD patients, single nucleotide polymorphisms in BIN1 correlate well with tau pathology, suggesting the involvement of BIN1 in the formation and propagation of tau accumulation pathology, but the molecular mechanism and point of action remain unclear.

Method: To comprehensively clarify the effects of BIN1 on two pathological events, tau aggregation and propagation, we analyzed BIN1 knockout mice.

Basic Science and Pathogenesis.

Background: Tau aggregation is the major cause of several neurodegenerative tauopathies. Tau interaction with other proteins affects the formation of tau aggregates with seeding activity but less is known about its effects on tau-seed properties. Our previous study revealed that Bassoon (BSN), a presynaptic protein, interacts with tau-seed, exacerbating its toxicity in vivo.

Basic Science and Pathogenesis.

Background: We researched the occurrence, neuropathology, and clinical features of spastic paraplegia (SP) associated to dementia in presenilin 1 (PSEN1) Italian patients related to familial Alzheimer's disease (AD).

Methods: We carried out whole exome sequencing in 33 familial AD probands with hereditary spastic paraplegia (HSP) that resulted negative for the identification of pathogenetic variants in known HSP genes. One patient was identified with a DNA variant in PSEN1, and bioinformatic analysis was conducted to characterize its pathogenetic nature.

Clinical Manifestations.

Background: Despite the clinical importance and significant social burden of neuropsychiatric symptoms (NPS) in dementia, the underlying neurobiological mechanism remains poorly understood. Recently, neuroimaging-derived brain-age estimation by machine-learning analysis has shown promise as an individual-level biomarker. We investigated the relationship between NPS and brain-age in amnestic mild cognitive impairment (MCI) and early dementia.

Clinical Manifestations.

Background: Objective and sensitive measures of everyday function are needed for accurate clinical diagnosis and evaluation of outcomes in clinical trials for dementia. However, most objective everyday function measures are difficult to administer and have not been validated against biomarkers of Alzheimer's disease (AD) neuropathology. This study evaluated the neuroimaging correlates of a highly sensitive, ecologically valid, and easily implementable performance-based test of function called the Virtual Kitchen Challenge (VKC).

Clinical Manifestations.

Background: Gait performance has been found to be an effective method for screening cognitive impairment in elderly. Nevertheless, the efficacy of utilizing gait speed as a marker for monitoring cognitive changes remains incompletely substantiated.

Method: From 2021 to 2023, we recruited 104 participants from the memory clinic of Cardinal Tien Hospital in Taipei, Taiwan.

Clinical Manifestations.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative condition, with considerable variation in disease progression from the mild cognitive impairment (MCI) stage. Predicting disease progression will support prognostic decisions and patient management. Here we designed a machine learning (ML) stack model, where a classifier was used to differentiate MCI progressors from non-progressors (i.

Impact of technological advancements on short-term outcomes in flap reconstruction after soft tissue sarcoma resection: A retrospective comparative analysis.

Background: Soft tissue sarcomas (STS) are rare malignancies requiring extensive surgical resection, often leading to significant soft tissue defects. Flap reconstruction is crucial for restoring function and appearance. Recent reconstructive microsurgery advancements, including high-resolution indocyanine green (ICG) imaging and ultra-high-frequency ultrasonography (UHFU), have revolutionized preoperative planning and intraoperative guidance.

Efficacy and tolerability of lacosamide in pediatric and young adult epilepsy patients with severe motor and intellectual disabilities.

Objective: Epilepsy is common among patients with severe motor and intellectual disability (SMID) patients, often taking a prolonged and intractable course. Lacosamide (LCM) is widely used to treat epilepsy in both adults and children. We assess the efficacy and tolerability of LCM among pediatric and young adult epilepsy patients with SMID who suffer from intractable seizures.

Intraoperative Skull Fracture During Halo Application in Subcranial Le Fort III: Strategies for Managing a Rare Complication.

External rigid distraction is an established method for achieving subcranial Le Fort III advancement in severe syndromic craniosynostosis. Craniofacial surgeons commonly use halo-type devices for these corrections, as they allow for multiple vectors of pull and facilitate larger midfacial advancements. Although most complications related to their use involve pin displacement or infection, rare complications such as skull fractures have been reported.