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.

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.

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.

Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity.

Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD).

Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes.

Design, Setting, And Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024.

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.

Comparison of accumulation rates of beta-amyloid tracers and their relationship with cognitive changes.

We aimed to compare amyloid-β (Aβ) accumulation rates between different tracers and investigate whether the relationship between changes in Aβ uptake and cognitive decline varies depending on tracer type. Two cohorts were analyzed: (1) a head-to-head longitudinal cohort using F-Florbetaben (FBB) and F-Flutemetamol (FMM) tracers (n = 13), and (2) separate longitudinal cohorts for each tracer (n = 174 for both FMM and FBB), matched by propensity score. Aβ uptake was measured using regional direct comparison of Centiloid (rdcCL) values.

Temporal Dynamics and Biological Variability of Alzheimer Biomarkers.

Importance: Understanding the characteristics of discordance between plasma biomarkers and positron emission tomography (PET) results in Alzheimer disease (AD) is crucial for accurate interpretation of the findings.

Objective: To compare (1) medical comorbidities affecting plasma biomarker concentrations, (2) imaging and clinical features, and (3) cognitive changes between plasma biomarker and PET discordant and concordant cases.

Design, Setting, And Participants: This multicenter cohort study, conducted between 2016 and 2023, included individuals with unimpaired cognition, mild cognitive impairment, or Alzheimer-type dementia, who had both amyloid β (Aβ) PET imaging and plasma biomarkers.

Differential roles of Alzheimer's disease plasma biomarkers in stepwise biomarker-guided diagnostics.

Introduction: This study aimed to investigate the differential roles of various plasma biomarkers in a stepwise diagnostic strategy for Alzheimer's disease (AD).

Methods: A total of 2984 participants, including 666 cognitively unimpaired (CU), 2032 with Alzheimer's clinical syndrome (ACS), and 286 non-ACS individuals, were recruited. Plasma amyloid beta (Aβ) 42/40, four phosphorylated tau (p-tau) epitopes, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels were measured using immunoassays.

Association between focal amyloid deposition and cognitive impairment in individuals below the amyloid threshold.

Purpose: This study aimed to investigate the characteristics of individuals with amyloid levels below the threshold. To achieve this, we differentiated between two groups: those with global amyloid negativity but focal deposition [G(-)F(+)] and those without focal deposition [G(-)F(-)].

Materials And Methods: A total of 2,677 participants were diagnosed with cognitive unimpairment (CU) or mild cognitive impairment (MCI).

Plasma Alzheimer's disease biomarker variability: Amyloid-independent and amyloid-dependent factors.

Introduction: We aimed to investigate which factors affect plasma biomarker levels via amyloid beta (Aβ)-independent or Aβ-dependent effects and improve the predictive performance of these biomarkers for Aβ positivity on positron emission tomography (PET).

Methods: A total of 2935 participants underwent blood sampling for measurements of plasma Aβ42/40 ratio, phosphorylated tau 217 (p-tau217; ALZpath), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels using single-molecule array and Aβ PET. Laboratory findings were collected using a routine blood test battery.

Difference in trajectories according to early amyloid accumulation in cognitively unimpaired elderly.

Background And Purpose: Amyloid β (Aβ), a major biomarker of Alzheimer's disease, leads to tau accumulation, neurodegeneration and cognitive decline. Modelling the trajectory of Aβ accumulation in cognitively unimpaired (CU) individuals is crucial, as treatments targeting Aβ are anticipated. The evolution of Aβ levels was investigated to determine whether it could lead to classification into different groups by studying longitudinal Aβ changes in older CU individuals, and differences between the groups were compared.

Different associations between body mass index and Alzheimer's markers depending on metabolic health.

Background: Increasing evidence supports the association between body mass index (BMI), Alzheimer's disease, and vascular markers. Recently, metabolically unhealthy conditions have been reported to affect the expression of these markers. We aimed to investigate the effects of BMI status on Alzheimer's and vascular markers in relation to metabolic health status.

Prediction of Amyloid Positivity in Patients with Subcortical Vascular Cognitive Impairment.

Background: Amyloid-β (Aβ) commonly coexists and impacts prognosis in subcortical vascular cognitive impairment (SVCI).

Objective: This study aimed to examine the differences in clinical and neuroimaging variables between Aβ-positive and Aβ-negative SVCI and to propose a prediction model for Aβ positivity in clinically diagnosed SVCI patients.

Methods: A total of 130 patients with SVCI were included in model development, and a separate cohort of 70 SVCI patients was used in external validation.

Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea.

Background: Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear.