Cutting through the noise: A narrative review of Alzheimer's disease plasma biomarkers for routine clinical use.

As novel, anti-amyloid therapies have become more widely available, access to timely and accurate diagnosis has become integral to ensuring optimal treatment of patients with early-stage Alzheimer's disease (AD). Plasma biomarkers are a promising tool for identifying AD pathology; however, several technical and clinical factors need to be considered prior to their implementation in routine clinical use. Given the rapid pace of advancements in the field and the wide array of available biomarkers and tests, this review aims to summarize these considerations, evaluate available platforms, and discuss the steps needed to bring plasma biomarker testing to the clinic.

Predicting regional tau accumulation with machine learning-based tau-PET and advanced radiomics.

Introduction: Alzheimer's disease is partially characterized by the progressive accumulation of aggregated tau-containing neurofibrillary tangles. Although the association between accumulated tau, neurodegeneration, and cognitive decline is critical for disease understanding and clinical trial design, we still lack robust tools to predict individualized trajectories of tau accumulation. Our objective was to assess whether brain imaging biomarkers of flortaucipir-positron emission tomography (PET), in combination with clinical and genomic measures, could predict future pathological tau accumulation.

Application of the revised criteria for diagnosis and staging of Alzheimer's disease: Drug development and clinical practice.

Unlabelled: The newly proposed revised criteria for diagnosis and staging of Alzheimer's disease (AD) by the Alzheimer's Association (AA) Workgroup represent a significant milestone in the field. These criteria offer objective measures for diagnosing and staging biological AD, bridging the gap between research and clinical care. Although implementation feasibility may vary across regions and settings, improving the availability and accuracy of biomarkers, especially plasma biomarkers, is expected to enhance the applicability of these criteria in clinical practice.

ADNI Biomarker Core: A review of progress since 2004 and future challenges.

Background: We describe the Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core major activities from October 2004 to March 2024, including biobanking ADNI cerebrospinal fluid (CSF), plasma, and serum biofluid samples, biofluid analyses for Alzheimer's disease (AD) biomarkers in the Biomarker Core and various non-ADNI laboratories, and continuous assessments of pre-analytics.

Results: Validated immunoassay and mass spectrometry-based assays were performed in CSF with a shift to plasma, a more accessible biofluid, as qualified assays became available. Performance comparisons across different CSF and plasma AD biomarker measurement platforms have enriched substantially the ADNI participant database enabling method performance determinations for AD pathology detection and longitudinal assessments of disease progression.

Advantages of Lissamine Green Vital Staining as an Endpoint in Dry Eye Clinical Trials.

Purpose: The absence of a standardized diagnostic method for clinical signs of Dry Eye Disease (DED) complicates clinical trials for future treatments. This paper evaluated Lissamine Green (LG) conjunctival staining as a valid, stable and modifiable endpoint for both clinical practice and clinical trials.

Methods: Screening and pre-randomization data from two identically designed clinical trials for DED resulted in a pooled dataset of 494 subjects.

Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly.

Background: Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD.

Methods: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study.

A review of the flortaucipir literature for positron emission tomography imaging of tau neurofibrillary tangles.

Alzheimer's disease is defined by the presence of β-amyloid plaques and neurofibrillary tau tangles potentially preceding clinical symptoms by many years. Previously only detectable post-mortem, these pathological hallmarks are now identifiable using biomarkers, permitting an definitive diagnosis of Alzheimer's disease. F-flortaucipir (previously known as F-T807; F-AV-1451) was the first tau positron emission tomography tracer to be introduced and is the only Food and Drug Administration-approved tau positron emission tomography tracer (Tauvid™).

Voices from the field: exploring service providers' insights into service delivery and AAC use in Canada.

Use of augmentative and alternative communication (AAC) often relies on the involvement of AAC service providers; however little is known about how AAC services are delivered across Canada. This study aimed to explore AAC service provision and factors influencing use of AAC from the perspectives of service providers across Canada who are involved in providing and/or supporting use of AAC systems. The 22 participants from nine (of the 10) provinces participated in online focus groups.

Novel Alzheimer's disease genes and epistasis identified using machine learning GWAS platform.

Alzheimer's disease (AD) is a complex genetic disease, and variants identified through genome-wide association studies (GWAS) explain only part of its heritability. Epistasis has been proposed as a major contributor to this 'missing heritability', however, many current methods are limited to only modelling additive effects. We use VariantSpark, a machine learning approach to GWAS, and BitEpi, a tool for epistasis detection, to identify AD associated variants and interactions across two independent cohorts, ADNI and UK Biobank.

Canadian manufacturer and technician perspectives on the design and use of augmentative and alternative communication technology.

Purpose: Device manufacturers and technicians (MaTs) of augmentative and alternative communication (AAC) systems play key roles in the design and successful uptake of communication devices. This study aims to investigate MaT perspectives on AAC device design and effective use.

Materials And Methods: To investigate their perspectives, a focus group of MaTs within Canada was conducted.

Models and frameworks for guiding assessment for aided Augmentative and Alternative communication (AAC): a scoping review.

Background: Augmentative and Alternative Communication (AAC) supports individuals with complex communication needs. Conceptual models and frameworks exist to evaluate, implement, and assess the needs of persons with communication disabilities, however, it is unknown which models were grounded in previous evidence-based research.

Objective: What are the models and frameworks grounded in empirical or conceptual research that enable communication outcomes for persons who require aided AAC systems?

Eligibility Criteria: The study had to be the original publication of a defined model or framework that included aided AAC and the model had to be developed through research, either conceptual or empirical.

Diagnostic Biomarkers of Amyloid and Tau Pathology in Alzheimer's Disease: An Overview of Tests for Clinical Practice in the United States and Europe.

Amyloid and tau biomarkers for Alzheimer's disease are widely recognized diagnostic tools for the identification of Alzheimer's disease pathology antemortem and are recommended by the most recent clinical and research guidelines. Approved biomarkers include positron emission tomography (PET)- and fluid-based markers derived from cerebrospinal fluid and, more recently, plasma. These biomarkers are still infrequently used in clinical practice, potentially due to challenges in access to and understanding of individual assay information and methodology.

Plasma Glial Fibrillary Acidic Protein Is Associated with 18F-SMBT-1 PET: Two Putative Astrocyte Reactivity Biomarkers for Alzheimer's Disease.

Background: Astrocyte reactivity is an early event along the Alzheimer's disease (AD) continuum. Plasma glial fibrillary acidic protein (GFAP), posited to reflect astrocyte reactivity, is elevated across the AD continuum from preclinical to dementia stages. Monoamine oxidase-B (MAO-B) is also elevated in reactive astrocytes observed using 18F-SMBT-1 PET in AD.

β-amyloid PET harmonisation across longitudinal studies: Application to AIBL, ADNI and OASIS3.

Introduction: The Centiloid scale was developed to harmonise the quantification of β-amyloid (Aβ) PET images across tracers, scanners, and processing pipelines. However, several groups have reported differences across tracers and scanners even after centiloid conversion. In this study, we aim to evaluate the impact of different pre and post-processing harmonisation steps on the robustness of longitudinal Centiloid data across three large international cohort studies.

Visually Identified Tau 18F-MK6240 PET Patterns in Symptomatic Alzheimer's Disease.

Background: In Alzheimer's disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice.

Objective: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using 18F-MK6240, and whether these patterns are associated with different demographic and cognitive profiles.

Assessment of a polygenic hazard score for the onset of pre-clinical Alzheimer's disease.

Background: With a growing number of loci associated with late-onset (sporadic) Alzheimer's disease (AD), the polygenic contribution to AD is now well established. The development of polygenic risk score approaches have shown promising results for identifying individuals at higher risk of developing AD, thereby facilitating the development of preventative and therapeutic strategies. A polygenic hazard score (PHS) has been proposed to quantify age-specific genetic risk for AD.

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume.

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer's Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Plasma p217+tau versus NAV4694 amyloid and MK6240 tau PET across the Alzheimer's continuum.

Introduction: We evaluated a new Simoa plasma assay for phosphorylated tau (P-tau) at aa217 enhanced by additional p-tau sites (p217+tau).

Methods: Plasma p217+tau levels were compared to F-NAV4694 amyloid beta (Aβ) positron emission tomography (PET) and F-MK6240 tau PET in 174 cognitively impaired (CI) and 223 cognitively unimpaired (CU) participants.

Results: Compared to Aβ- CU, the plasma levels of p217+tau increased 2-fold in Aβ+ CU and 3.

Mesial temporal tau in amyloid-β-negative cognitively normal older persons.

Background: Tau deposition in the mesial temporal lobe (MTL) in the absence of amyloid-β (Aβ-) occurs with aging. The tau PET tracer F-MK6240 has low non-specific background binding so is well suited to exploration of early-stage tau deposition. The aim of this study was to investigate the associations between MTL tau, age, hippocampal volume (HV), cognition, and neocortical tau in Aβ- cognitively unimpaired (CU) individuals.

First-in-Humans Evaluation of F-SMBT-1, a Novel F-Labeled Monoamine Oxidase-B PET Tracer for Imaging Reactive Astrogliosis.

Reactive gliosis, characterized by reactive astrocytes and activated microglia, contributes greatly to neurodegeneration throughout the course of Alzheimer disease (AD). Reactive astrocytes overexpress monoamine oxidase B (MAO-B). We characterized the clinical performance of F-()-(2-methylpyrid-5-yl)-6-[(3-fluoro-2-hydroxy)propoxy]quinoline (F-SMBT-1), a novel MAO-B PET tracer as a potential surrogate marker of reactive astrogliosis.