Prognostic Value of A/T/N Biomarkers: Comparing Plasma and Imaging Modalities in Alzheimer Disease.

Background: Alzheimer disease (AD) is characterized by amyloid-β plaques (A), tau tangles (T), and neurodegeneration (N), collectively defining the ATN framework. While imaging biomarkers are well-established, the prognostic value of plasma biomarkers in predicting cognitive decline remains underexplored. This study compares plasma and imaging A/T/N biomarkers in predicting cognitive decline and evaluate the impact of combining biomarkers across modalities.

Mapping Alzheimer's disease pathology using free water through integrated analysis of plasma biomarkers, microstructural DTI metrics, and macrostructural MRI measures.

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) and tau pathologies that drive neuroinflammation and neurodegeneration. Free water (FW), a diffusion tensor imaging (DTI) metric reflecting extracellular fluid changes, has emerged as a sensitive marker of neuroinflammation. This study examined the role of FW in AD and its associations with plasma biomarkers, brain structural measures, and cognitive decline.

Integrating MRI Volume and Plasma p-Tau217 for Amyloid Risk Stratification in Early-Stage Alzheimer Disease.

Background And Objectives: Identifying β-amyloid (Aβ) positivity is crucial for selecting candidates for Aβ-targeted therapies in early-stage Alzheimer disease (AD). While Aβ PET is accurate, its high cost limits routine use. Plasma p-tau217 testing offers a less invasive option but also incurs additional costs.

Utility of the Seoul Cognitive Status Test to detect amyloid status in mild cognitive impairment.

BackgroundInvestigating amyloid-β (Aβ) status could offer clinical implications for the identification of and intervention for individuals at higher risk of dementia due to Alzheimer's disease (AD). The use of computerized cognitive tests has been considered valuable in detecting Aβ positivity.ObjectiveThis study aims to examine the predictive accuracy of the Seoul Cognitive Status Test (Seoul CST) for Aβ-positive mild cognitive impairment (Aβ+ MCI).

Plasma phosphorylated tau 217 and amyloid‑β 42/40 for amyloid risk in subgroups.

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) pathology. Recently, plasma biomarkers, particularly p-tau217, have emerged as promising tools for early diagnosis and risk stratification. In this retrospective study, we evaluated the diagnostic performance of p-tau217 combined with other plasma biomarkers in distinguishing Aβ Positron emission tomography (PET) positivity in cognitively unimpaired (CU) and cognitively impaired (CI) individuals across diverse clinical subgroups.

Potential utility of plasma pTau217 for assessing amyloid and tau biomarker profiles.

Purpose: Plasma phosphorylated tau 217 (pTau217) is a promising biomarker for Alzheimer's disease, reflecting both amyloid β (Aβ) and tau positron emission tomography (PET) results. While its diagnostic role is actively being investigated, this study aims to expand its application to staging disease progression and predicting cognitive decline.

Methods: A total of 2,919 participants, primarily diagnosed as Alzheimer's clinical syndrome, were recruited.

A novel deep learning-based brain age prediction framework for routine clinical MRI scans.

Physiological brain aging is associated with cognitive impairment and neuroanatomical changes. Brain age prediction of routine clinical 2D brain MRI scans were understudied and often unsuccessful. We developed a novel brain age prediction framework for clinical 2D T1-weighted MRI scans using a deep learning-based model trained with research grade 3D MRI scans mostly from publicly available datasets (N = 8681; age = 51.

Re-evaluation of arterial dissection as a possible major cause of lateral medullary infarction in a single-center study from South Korea.

Limited sensitivity of conventional MRI and the invasiveness of TFCA have restricted the diagnosis of arterial dissection in lateral medullary infarction (LMI), leading to its underestimation and obscuring its clinical significance. However, high-resolution vessel wall MRI (HR-VWMRI) now allows more accessible and accurate diagnosis of dissection, prompting reevaluation of its prevalence. This single-center retrospective study included the LMI patients, among whom a subset underwent advanced imaging as HR-VWMRI or TFCA to confirm definite arterial dissection, and identified clinical factors associated with dissection.

Erratum: Clinicopathological Correlations of Neurodegenerative Diseases in the National Brain Biobank of Korea.

This corrects the article on p. 190 in vol. 21, PMID: 40308014.

Diverse Clinical Phenotypes of Neuronal Intranuclear Inclusion Disease in South Korea.

Background And Purpose: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by a wide range of clinical manifestations. GGC-repeat expansion in was recently identified as the genetic cause of NIID. Here we report clinical, radiological, pathological, and genetic findings in NIID patients.

Validation of criteria for frontotemporal dementia with right anterior temporal lobe predominance.

Introduction: Frontotemporal dementia (FTD) with right anterior temporal lobe (rATL) predominance lacks universally agreed-upon diagnostic criteria. This study validated the Amsterdam diagnostic tree (ADT) for right temporal variant FTD (rtvFTD) and the diagnostic criteria for semantic behavioral variant FTD (sbvFTD), examining clinical, behavioral, and imaging differences.

Methods: The study included 138 patients with behavioral variant FTD and 87 with semantic variant primary progressive aphasia who had 3D T1-weighted magnetic resonance imaging scans.

Integrating visual assessments and quantification methods for tau PET staging.

Introduction: We compared visual assessments and quantification methods for tau positron emission tomography (PET) staging and evaluated plasma biomarkers and cognitive trajectories across amyloid and tau (AT) staging.

Methods: Tau PET scans from 289 Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) participants were analyzed visually and quantitatively, with validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n = 870). Plasma biomarkers and cognitive measures were evaluated across AT stages.

Effect modification by cardiovascular and metabolic disease onset on long-term PM exposure and mortality: a nationwide cohort study.

Cardiovascular and metabolic diseases-specifically myocardial infarction, congestive heart failure, cerebrovascular disease, peripheral vascular disease, renal disease, and liver disease-are major public health concerns worldwide. However, studies examining how these diseases modify the relationship between long-term PM exposure and mortality remain scarce. Using a Cox regression model with a population-representative cohort from South Korea, we estimated the modifying effects of six major cardiovascular and metabolic diseases on PM-mortality association in two cohorts: (1) individuals without underlying diseases (NoUD) and (2) those with only hypertension and/or diabetes (HTN/DM).

Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer's disease and a cumulative effects model for risk liability.

Genome-wide association studies (GWAS) on Alzheimer's disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (APCDD1) associated with AD.

Tailoring thresholds for interpreting plasma p-tau217 levels.

Background: Plasma phosphorylated tau (p-tau) 217 test has emerged as a minimally invasive and accessible alternative to positron emission tomography imaging and cerebrospinal fluid analysis for Alzheimer's disease (AD) diagnostics. However, the diagnostic performance of p-tau217 across diverse cognitive and demographic subgroups remains underexplored. This multicentre cross-sectional study aimed to assess the diagnostic utility of plasma p-tau217 using a double cut-off approach in a large, diverse cohort, focusing on subgroup analyses based on cognitive status, age, sex, body mass index and ε4 carrier status.

Cerebral Amyloid Angiopathy and Downstream Alzheimer Disease Plasma Biomarkers.

Importance: As amyloid-targeted therapies have become commercially available, the monitoring of cerebral amyloid angiopathy (CAA), which is an important risk factor for amyloid-related imaging abnormalities, has received increasing attention. However, comprehensive evidence on the association between Alzheimer disease (AD) plasma biomarkers and various CAA imaging markers is still lacking.

Objective: To examine the association of CAA imaging markers with downstream AD plasma biomarkers in relation to amyloid-β (Aβ) uptake on positron emission tomography (PET) and whether their interplay is associated with cognitive changes.

Reproducibility of Plasma Biomarker Measurements Across Laboratories: Insights Into ptau217, GFAP, and NfL.

Background And Purpose: Plasma biomarkers, including phosphorylated tau (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL), are promising tools for detecting Alzheimer's disease (AD) pathology. However, cross-laboratory reproducibility remains a challenge, even when using identical analytical platforms such as single-molecule array (Simoa). This study aimed to compare plasma biomarker measurements (ptau217, GFAP, and NfL) between 2 laboratories, the University of Gothenburg (UGOT) and DNAlink, and evaluate their associations with amyloid positron emission tomography (PET) imaging.

Comprehensive Clinical and Behavioral Characteristics of Mild Cognitive Impairment According to Amyloid Positivity: A Large Multi-Center Korean Cohort.

Background And Purpose: Mild cognitive impairment (MCI) is a transitional stage to dementia, Alzheimer's disease being a major cause. Although amyloid beta-positive (Aβ+) MCI has been well-characterized, Aβ-negative (Aβ-) MCI has not. This study compared the comprehensive clinical and behavioral characteristics of Aβ+ and Aβ- MCI in a large multi-center cohort to better understand the heterogeneity of MCI, and to identify contributing factors to cognitive impairment.

Establishing Regional Aβ Cutoffs and Exploring Subgroup Prevalence Across Cognitive Stages Using BeauBrain Amylo.

Background And Purpose: Amyloid-beta (Aβ) plaques are key in Alzheimer's disease (AD), with Aβ positron emission tomography imaging enabling non-invasive quantification. To address regional Aβ deposition, we developed regional Centiloid scales (rdcCL) and commercialized them through the computed tomography (CT)-based BeauBrain Amylo platform, eliminating the need for three-dimensional T1 magnetic resonance imaging (MRI).

Objective: We aimed to establish robust regional Aβ cutoffs using the commercialized BeauBrain Amylo platform and to explore the prevalence of subgroups defined by global, regional, and striatal Aβ cutoffs across cognitive stages.

Clinicopathological Correlations of Neurodegenerative Diseases in the National Brain Biobank of Korea.

Background And Purpose: The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK.

Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB).

Cross-ancestry genome-wide association study identifies implications of SORL1 in cerebral beta-amyloid deposition.

GWAS of Alzheimer's disease have been predominantly based on European ancestry cohorts with clinically diagnosed patients. Increasing the ancestral diversity of GWAS and focusing on imaging brain biomarkers for Alzheimer's disease may lead to the identification of new genetic loci. Here, we perform a GWAS on cerebral β-amyloid deposition measured by PET imaging in 3,885 East Asians and a cross-ancestry GWAS meta-analysis with data from 11,816 European participants.

Evaluation of AAV transduction efficiency via multiple delivery routes: Insights from peripheral and central nervous system analysis.

This study evaluates the biodistribution and transduction efficiency of adeno-associated virus serotype 9 (AAV9) vectors administered via intracerebroventricular (ICV), intra-arterial (IA), and intravenous (IV) routes in a murine model. Quantitative assessments of green fluorescent protein (GFP) expression were conducted to compare transduction efficacy across central nervous system (CNS) and peripheral tissues. The results demonstrate that high-dose ICV administration resulted in robust GFP expressions in the hippocampus and fimbria, indicating effective CNS targeting.

Effects of Dexamethasone and Tacrolimus on Mesenchymal Stem Cell Characteristics and Gene Expression.

Mesenchymal stem cells (MSCs) are frequently used for therapeutic applications in both pre-clinical and clinical settings owing to their capacity for immune modulation and neuroprotective effects. However, transient fever is commonly observed as an adverse event following MSC injection in patients with Alzheimer's disease (AD). In this study, we investigated the potential impact of immunosuppressants such as dexamethasone and tacrolimus on altering the characteristics of human mesenchymal stem cells (hMSCs).

Physical Activity, Alzheimer Plasma Biomarkers, and Cognition.

Importance: Physical activity (PA) is a nonpharmacological intervention for dementia prevention. The association between PA and Alzheimer disease (AD) plasma biomarkers remains underexplored.

Objective: To investigate the associations among PA; plasma biomarkers, including β-amyloid 42/40 (Aβ42/40), phosphorylated-tau217 (ptau217), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL); and cognition.