Keun-A Chang

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss, ultimately leading to a loss of independence and reduced quality of life. As current treatments are most effective in the early stages, reliable blood-based biomarkers are required for early diagnosis, therapeutic monitoring, and disease staging. Plasma neurofilament light chain (NfL), a marker of neuroaxonal injury, is a candidate biomarker; its value relative to established amyloid- and tau-based biomarkers is unclear. A systematic review and meta-analysis comparing plasma NfL with Aβ42, Aβ40, the Aβ42/Aβ40 ratio, and p-tau217 across cognitively normal (control, Con), mild cognitive impairment (MCI), and AD groups was conducted. Fourteen studies that met specific criteria were included. Plasma NfL and p-tau217 increased across disease stages. Aβ42 and Aβ42/Aβ40 were lower in AD/MCI than in Con; Aβ40 was similar across groups. Heterogeneity (I² < 99%) was observed across biomarkers. Plasma NfL reliably reflected neuroaxonal injury and disease severity from the earliest clinically detectable stage of AD. Plasma NfL may be most valuable when combined with p-tau217/Aβ-based assays to provide a more comprehensive, blood-based assessment of both AD-specific pathology and neurodegeneration. Further studies are needed to validate its prognostic utility and establish clinically applicable cut-off values.

Alzheimer's disease (AD) is characterized by progressive cognitive decline accompanied by synaptic dysfunction and neuronal loss. Dysregulation of specific microRNAs (miRNAs) has been increasingly implicated in AD pathogenesis, suggesting that miRNA-mediated regulatory pathways may represent important mechanisms underlying neuronal vulnerability. Here, we identified mmu-microRNA-204-5p (miR-204) as a critical regulator of neuronal survival that is markedly downregulated in the hippocampus of 5xFAD mice. Through integrated bioinformatics analysis and experimental validation, we established neuronal pentraxin-1 (NPTX1) as a direct post-transcriptional target of miR-204. In primary cultured neurons, exposure to Aβ₁₋₄₂ oligomer (oAβ) drove marked upregulation of NPTX1 and precipitated neuronal injury, manifested by aberrant reactive oxygen species (ROS) accumulation, collapse of mitochondrial membrane potential, diminished cell viability, and dendritic degeneration. Inhibition of miR-204 further exacerbated these pathological changes and engaged mitochondrial apoptotic signaling, as evidenced by Bax upregulation, cytochrome c release, and caspase-3 cleavage. Conversely, restoration of miR-204 expression or genetic knockdown of NPTX1 attenuated oxidative stress, preserved mitochondrial integrity, and restored neuronal survival. Collectively, our findings uncover a previously unrecognized miR-204-NPTX1 regulatory axis that governs mitochondrial integrity and apoptotic susceptibility in AD, highlighting miR-204 as a potential therapeutic target for AD and related oxidative stress-associated neurodegenerative disorders.

The prevalence of major depressive disorder (MDD) in young adulthood has increased in recent decades and represents a leading cause of psychological burden, highlighting the importance of prevention and early intervention for depression in young adults. Early-life stress has been closely associated with the onset of depression in young adulthood, leading to adverse outcomes, including reduced quality of life, impaired social functioning, and socioeconomic burden. Among the various neuropathological features of depression, astrocytic abnormalities are increasingly recognized as key contributors. Therefore, we aimed to investigate the association between dysregulated astrocyte expression and depression in young adults. We utilized CPMS (cumulative mild prenatal stress, maternal separation and social defeat) mice as a young adult depression model, in which animals were exposed to a cumulative mild stress (CMS) paradigm during development, including prenatal stress, maternal separation, and social defeat. We further categorized CPMS mice into susceptible and resilient groups based on social interaction behavior. To explore the translational relevance of our findings, we subsequently analyzed blood samples from drug-naïve patients with MDD in young adulthood (mean age of 24 years). CPMS-susceptible mice of both sexes exhibited anxiety- and depression-like behaviors, accompanied by reduced expression of astrocytic markers in the prefrontal cortex. Furthermore, elevated S100B protein levels were observed in the blood of both CPMS mice and patients, showing a positive correlation with the severity of clinical symptoms. Together, these findings indicate that exposure to CMS during early life is associated with altered astrocytic protein expression and elevated circulating S100B, highlighting its potential relevance as a biomarker for depression in young adulthood.

Polymer-engineered MXene composites have emerged as a versatile materials platform for electrochemical energy storage, offering a means to address key limitations associated with ion transport, structural instability, and interfacial reactivity. This review provides a unified perspective on how polymer integration modifies the structure–transport–stability relationships of MXene-based systems across Na-ion batteries, aqueous Zn-ion batteries, and supercapacitors. In Na-ion systems, polymer-mediated interlayer engineering and porosity control improve ion accessibility and mitigate diffusion limitations arising from the large ionic radius of Na⁺. In aqueous Zn-ion systems, polymer electrolytes and interfacial layers regulate Zn²⁺ solvation and deposition behavior, suppressing dendritic growth and parasitic reactions. In supercapacitors, polymer–MXene hybrids establish coupled ionic–electronic transport pathways and mechanically compliant architectures, enabling stable electrochemical performance under high-rate and deformable conditions. Particular emphasis is placed on the underlying mechanisms responsible for suppressing oxidation, preserving structural integrity, and extending cycle life, including interfacial passivation, desolvation regulation, and structural confinement. These coupled effects govern long-term electrochemical stability across different energy storage systems. Finally, recent advances in operando characterization, data-driven materials design, and scalable processing are discussed in the context of future development. By linking material design strategies to fundamental mechanisms, this review outlines a coherent framework for the rational development of polymer–MXene composites toward practical energy storage applications.

Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) accumulation, neuroinflammation, synaptic dysfunction, and cognitive decline. Impairment of microglial autophagy-lysosomal pathway (ALP) is increasingly recognized as a key driver of the disease progression. Transcription factor EB (TFEB), a master regulator of ALP, has emerged as a promising therapeutic target; however, its specific role in microglia remains unclear. Here, we aimed to determine the therapeutic effects of microglial TFEB expression in AD pathogenesis. We established a tamoxifen-inducible, microglia-specific TFEB-overexpressing 5xFAD mouse line (5xTFEB) and conducted behavioural testing, histopathology and biochemical analyses, live-cell imaging of Aβ phagocytosis, and bulk RNA sequencing. Differential gene expressions were analysed, and inflammasome activation was evaluated. Microglial TFEB overexpression restored ALP function, promoted phagolysosomal clearance of oligomeric Aβ, and reduced the amyloid burden in the cortex, hippocampus, and entorhinal cortex of the 5xFAD mice. These changes rescued memory deficits in both male and female 5xTFEB mice. Transcriptomic profiling revealed upregulation of ALP and downregulation of inflammatory signalling. Additionally, inflammasome activation was attenuated in 5xTFEB mice. Targeted TFEB activation in microglia reprograms degradative and immune pathways, enhancing Aβ clearance while alleviating neuroinflammation and cognitive impairment in AD. Overall, microglial TFEB modulation is a promising cell-type–specific therapeutic strategy for AD and related neurodegenerative disorders. Graphical abstract

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, ultimately leading to loss of independence and reduced quality of life. Since current treatments are most effective in early stages, the development of reliable and noninvasive biomarkers for early diagnosis and monitoring is crucial. Abnormal tau protein aggregation is a key pathological hallmark of AD, disrupting neuronal integrity, accelerating progression, and associating closely with cognitive decline and the transition to mild cognitive impairment, a prodromal stage of AD. Currently, tau pathology is evaluated mainly by cerebrospinal fluid analysis and tau positron emission tomography (tau PET), which are invasive or costly, limiting their clinical applicability. This systematic review and meta-analysis synthesized evidence on tau as a blood-based biomarker for dementia, with emphasis on its relationship to tau PET, the gold standard for in vivo tau assessment. Findings indicate that elevated plasma tau levels such as p-tau181, p-tau217 and p-tau231 consistently reflect brain tau pathology, supporting their role as surrogate markers. Large-scale longitudinal validation is warranted to establish blood-based tau as a practical, accessible tool for early detection and disease monitoring, thereby improving therapeutic outcomes in AD.

Background: Lysosomal dysfunction could be an underlying cause of Alzheimer's disease, with Tau oligomer being an important inducer or amplifier of lysosomal stress associated with the disease. Tau oligomer is a well-known substrate of autophagy, and selective degradation of Tau with Tau-specific autophagy degrader might be feasible.

Stroke affects over 12 million people annually, leading to high mortality, long-term disability, and substantial healthcare costs. Although East Asian herbal medicines are widely used for stroke treatment, the pathways of operation they use remain poorly understood. Our study investigates the neuroprotective properties of Astragalus mongholicus (AM) in acute ischemic stroke using photothrombotic (PTB) and transient middle cerebral artery occlusion (tMCAO) mouse models, as well as an in vitro oxygen-glucose deprivation (OGD) model. Post-OGD treatment with AM improved cell viability in mouse neuroblastoma cells, likely by reducing reactive oxygen species (ROS). Mice received short-term (0–2 days) or long-term (0–27 days) AM treatment post-stroke. Infarct size was assessed using a 2,3,5-triphenyl tetrazolium chloride (TTC) staining procedure alongside magnetic resonance imaging (MRI). Neuroprotective metabolites including inositol (Ins), glycerophosphocholine+phosphocholine (GPc+ PCh), N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG), creatine + phosphocreatine (Cr+PCr), and glutamine+glutamate (Glx) were analyzed via magnetic resonance spectroscopy (MRS). Gliosis was assessed using GFAP and Iba-1 immunohistochemical markers, while neurological deficits were quantified with modified neurological severity scores (mNSS). Motor and cognitive functions were assessed using cylinder, rotarod, and novel object recognition (NOR) tests. AM treatment significantly reduced ischemic damage and improved neurological outcomes in both acute and chronic stages of PTB and tMCAO models. Additionally, AM increased neuroprotective metabolites levels, reduced gliosis, and decreased oxidative stress, as evidenced by reduced inducible nitric oxide synthase (iNOS). These findings highlight the antioxidant properties of AM and its strong therapeutic potential for promoting recovery after ischemic stroke by alleviating neurological deficits, reducing gliosis, and mitigating oxidative stress.