Optimizing timing and cost-effective use of plasma biomarkers in Alzheimer's disease.

Background And Objectives: Early and cost-effective identification of amyloid positivity is crucial for Alzheimer's disease (AD) diagnosis. While amyloid PET is the gold standard, plasma biomarkers such as phosphorylated tau 217 (pTau217) provide a potential alternative. This study evaluates the diagnostic accuracy of a combined-panel approach using machine learning models and evaluated the biomarker significance.

Innate Immunity-Guided Macrophage-Homing Nanoplatform for Oral Tumor Immunotherapy and Real-Time Deep-Tissue Imaging in Pre-Clinical Models.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and a high propensity for liver metastasis. This study presents an innate immunity-guided, macrophage (MΦ)-homing nanoplatform that enables oral delivery of theranostic agents to PDAC lesions by harnessing the migratory behavior of endogenous MΦ toward tumor-derived immune cues. The nanoplatform integrates a βGlus-R848 prodrug-constructed by conjugating β-glucans (βGlus) with the immunomodulator resiquimod (R848) via a reactive oxygen species (ROS)-responsive thioketal linker-and AgTe quantum dots (QDs) for near-infrared II (NIR-II) imaging, forming βGlus-R848/AgTe nanoparticles (NPs).

Development and validation of global tau severity score in Alzheimer's disease using Florzolotau (18F) PET.

Background: Tau-specific positron emission tomography (tau-PET) is valuable for assessing Alzheimer's disease (AD) severity, with phenotypic differences between young-onset AD (YOAD) and late-onset AD (LOAD) likely driven by distinct relationships between tau pathology and cognition.

Objective: This study developed a global tau severity (gTS) scale using Florzolotau (18F) PET and compared it with the CenTauR score for standardizing tau burden quantification.

Methods: A total of 186 participants were enrolled, including a pilot group (15 cognitive unimpaired controls [CTL], 15 AD patients) and a validation group (27 CTL, 67 YOAD, and 62 LOAD patients).

Asparagine deprivation enhances T cell antitumour response in patients via ROS-mediated metabolic and signal adaptations.

Preclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of L-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of L-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8T cell fitness.

Subcortical tau burden correlates with regional brain atrophy and plasma markers in four-repeat tauopathy parkinsonism.

BackgroundF-florzolotau positron emission tomography (PET) assists in the diagnosis of progressive supranuclear palsy (PSP).ObjectiveWe aimed to investigate the relationship between F-florzolotau uptake and clinical severity, structural volume changes, and plasma markers in four-repeat tauopathies.MethodsA total of 80 participants were recruited: 35 with PSP (11 with PSP-Richardson syndrome and 24 with PSP non-Richardson syndrome), 9 with corticobasal syndrome (CBS), 10 with Alzheimer's disease (AD), 8 with Parkinson's disease, and 18 controls.

The Taiwan-ADNI workflow toward integrating plasma p-tau217 into prediction models for the risk of Alzheimer's disease and tau burden.

Introduction: We integrated plasma biomarkers from the Taiwan Alzheimer's Disease Neuroimaging Initiative and propose a workflow to identify individuals showing amyloid-positive positron emission tomography (PET) with low/intermediate tau burden based on [18F]Florzolotau PET-based quantification.

Methods: We assessed 361 participants across the Alzheimer's disease (AD) and non-AD continuum and measured plasma phosphorylated tau (p-tau)217, p-tau181, amyloid beta (Aβ)42/40 ratio, neurofilament light chain, and glial fibrillary acidic protein levels at two medical centers. We evaluated the diagnostic potential of these biomarkers.

Macrophage-hitchhiked, effervescence-induced nanoemulsions for enhanced oral chemotherapy and immunotherapy: Impact on absorption route.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Paclitaxel (PTX), typically administered intravenously (IV) as chemotherapy, shows promise for triggering immunogenic cell death (ICD) and may serve as a potential immunotherapy. This study introduces an oral PTX delivery method using an enteric-coated gelatin capsule containing capric acid oil and an effervescent agent, optionally with decylamine-conjugated β-glucans (DA-βGlus).

Relationships among tumor necrosis factor-alpha levels, beta-amyloid accumulation, and hippocampal atrophy in patients with late-life major depressive disorder.

Background: Major depressive disorder (MDD) is characterized by hippocampal volume reduction, impacting cognitive function. Inflammation, particularly elevated tumor necrosis factor-alpha (TNF-α) levels, is consistently implicated in MDD pathophysiology. This study investigates the relationships between TNF-α levels, hippocampal volume, beta-amyloid (Aβ) burden, and cognitive abilities in MDD patients, aiming to illuminate the complex interplay among inflammatory markers, pathology indicators, structural brain alterations, and cognitive performance in non-demented MDD individuals.

Differences in Topography of Individual Amyloid Brain Networks by Amyloid PET Images in Healthy Control, Mild Cognitive Impairment, and Alzheimer's Disease.

Amyloid plaques, implicated in Alzheimer's disease, exhibit a spatial propagation pattern through interconnected brain regions, suggesting network-driven dissemination. This study utilizes PET imaging to investigate these brain connections and introduces an innovative method for analyzing the amyloid network. A modified version of a previously established method is applied to explore distinctive patterns of connectivity alterations across cognitive performance domains.

Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; = 55), late-onset AD (LOAD; = 96), TCP ( = 44), and cognitively unimpaired controls (CTL; = 90) and analyzed plasma Aβ42/Aβ40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity.

Distinct biological property of tau in tau-first cognitive proteinopathy: Evidence by longitudinal clinical neuroimaging profiles and compared with late-onset Alzheimer disease.

Background: Tau-first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status.

Aim: We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late-onset AD (LOAD).

Method: We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls.

Human biodistribution and radiation dosimetry for the tau tracer [F]Florzolotau in healthy subjects.

Background: Tau pathology plays a crucial role in neurodegeneration diseases including Alzheimer's disease (AD) and non-AD diseases such as progressive supranuclear palsy. Tau positron emission tomography (PET) is an in-vivo and non-invasive medical imaging technique for detecting and visualizing tau deposition within a human brain. In this work, we aim to investigate the biodistribution of the dosimetry in the whole body and various organs for the [F]Florzolotau tau-PET tracer.

Dominance of Tau Burden in Cortical Over Subcortical Regions Mediates Glymphatic Activity and Clinical Severity in PSP.

Background: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated.

Patients And Methods: Participants (n = 55; 65.

Classification Prediction of Alzheimer's Disease and Vascular Dementia Using Physiological Data and ECD SPECT Images.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common forms of dementia. However, their neuropsychological and pathological features often overlap, making it difficult to distinguish between AD and VaD. In addition to clinical consultation and laboratory examinations, clinical dementia diagnosis in Taiwan will also include Tc-99m-ECD SPECT imaging examination.

A low-energy emulsification platform based on a Diet Coke-Mentos reaction-derived bubbly flow for formulating various emulsions as drug carriers.

The formulation of a drug using high-energy emulsification commonly causes drug deterioration. Exploiting the well-known Diet Coke-Mentos reaction (DCMR), a U-shaped tube reactor that can generate an eruption of bubbly flow that can serve as a low-energy emulsification platform, is proposed. The liquid in the U-tube reactor is a supersaturated solution of aqueous CO, which mimics Diet Coke.

Visual reading for [F]Florzolotau ([F]APN-1607) tau PET imaging in clinical assessment of Alzheimer's disease.

Introduction: Tau-targeted positron emission tomography (tau-PET) is a potential tool for the differential diagnosis of Alzheimer's disease (AD) and to clarify the distribution of tau deposition. In addition to the quantitative analysis of tau-PET scans, visual reading supports the assessment of tau loading for clinical diagnosis. This study aimed to propose a method for visually interpreting tau-PET using the [F] Florzolotau tracer and investigate the performance and utility of the visual reading.

Plasmon-activated water as a therapeutic strategy in Alzheimer's disease by altering gut microbiota.

Gut microbiota (GM) are involved in the pathophysiology of Alzheimer's disease (AD) and might correlate to the machinery of the gut-brain axis. Alteration of the GM profiles becomes a potential therapy strategy in AD. Here, we found that plasmon-activated water (PAW) therapy altered GM profile and reduced AD symptoms in APPswe/PS1dE9 transgenic mice (AD mice).

Atrophy, hypometabolism and implication regarding pathology in late-life major depression with suspected non-alzheimer pathophysiology (SNAP).

Background: A substantial proportion of individuals with late-life major depression could be classified as having a suspected non-Alzheimer disease pathophysiology (SNAP), as indicated by a negative test for the biomarker β-amyloid (Aβ-) but a positive test for neurodegeneration (ND+). This study investigated the clinical features, characteristic patterns of brain atrophy and hypometabolism, and implications regarding pathology in this population.

Methods: Forty-six amyloid-negative patients with late-life major depressive disorder (MDD) patients, including 23 SNAP (Aβ-/ND+) and 23 Aβ-/ND- MDD subjects, and 22 Aβ-/ND-healthy control subjects were included in this study.

Decreased Cerebral Amyloid-β Depositions in Patients With a Lifetime History of Major Depression With Suspected Non-Alzheimer Pathophysiology.

Cerebral amyloid-β (Aβ) depositions in depression in old age are controversial. A substantial proportion of individuals with late-life major depressive disorder (MDD) could be classified as having suspected non-Alzheimer's disease pathophysiology (SNAP) by a negative test for the biomarker amyloid-β (Aβ-) but positive neurodegeneration (ND+). This study aimed to evaluate subthreshold Aβ loads in amyloid-negative MDD, particularly in SNAP MDD patients.