Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Biomarkers.

Background: As new anti-amyloid immunotherapies emerge for Alzheimer's disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P-tau217) for the detection of primary AD or AD co-pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: The performance of blood-based phosphorylated tau (pTau) immunoassays to detect asymptomatic Alzheimer's disease (AD) has important implications for therapeutic trials. pTau217 is often recommended as the preferred epitope due to its high fold changes in AD. The current study investigates the ability of a novel pTau217 assay to predict the dynamic phase of amyloid-β (Aβ) accumulation in comparison to the best-performing pTau181 assay.

Biomarkers.

Background: Neurodegenerative diseases are a heterogeneous group of illnesses. Differences across patients exist in the underlying biological drivers of disease. Furthermore, cross-diagnostic disease mechanisms exist, and different pathologies often co-occur in the brain.

Biomarkers.

Background: The retina, an integral part of the central nervous system, can exhibit protein accumulation (Aβ and pTau) associated with neurodegenerative diseases such as Alzheimer's disease (AD). Biochemical analysis revealed the existence of a distinct primary retinal tauopathy (PReT), differing from AD and primary age-related tauopathy (PART) brain lysates, suggesting it as a potential precursor for AD tauopathy with possible diagnostic value. However, it remains unclear whether retinal pTau pathology can spread from the eye into the brain.

Biomarkers.

Background: Synaptic dysfunction occurs in the early stages of neurodegenerative diseases and leads to the breakdown of connections within neuronal networks. Therefore, biomarkers reflecting this process, such as neurogranin (Ng), might be useful to study disease pathophysiology and aid in diagnostics. Ng is crucial for long-term potentiation and memory consolidation, and plays a central role in synaptic plasticity.

Biomarkers.

Background: Dementia with Lewy bodies (DLB) is a an α-synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB-related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis.

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

A weight of evidence review on the mode of action, adversity, and the human relevance of xylene's observed thyroid effects in rats.

Xylene substances have wide industrial and consumer uses and are currently undergoing dossier and substance evaluation under Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) for further toxicological testing including consideration of an additional neurotoxicological testing cohort to an extended one-generation reproduction toxicity (EOGRT) study. New repeated dose study data on xylenes identify the thyroid as a potential target tissue, and therefore a weight of evidence review is provided to investigate whether or not xylene-mediated changes on the hypothalamus-pituitary-thyroid (HPT) axis are secondary to liver enzymatic induction and are of a magnitude that is relevant for neurological human health concerns. Multiple published studies confirm xylene-mediated increases in liver weight, hepatocellular hypertrophy, and liver enzymatic induction the oral or inhalation routes, including an increase in uridine 5'-diphospho-glucuronosyltransferase (UDP-GT) activity, the key step in thyroid hormone metabolism in rodents.

Use and limitations of clinical data in the identification and classification of low molecular weight chemicals (LMWCs) as respiratory sensitizers: recommendations for improvement.

While progress has been made in recent years, there are still no suitable and accepted , or models that can be used to accurately predict whether a chemical substance has the intrinsic property to cause immune-mediated chemical respiratory allergy, typically manifested as allergic asthma or allergic rhinitis which represents a severe health hazard. Regulatory authorities have relied primarily on clinical evidence (case reports, clinical databases, worker exposure studies) to classify substances as respiratory sensitizers, but this evidence can lack a proven immunological mechanism which is necessary to identify substances which can cause life-long sensitization and clinically relevant allergic symptoms in the respiratory tract in an exposed population (such respiratory allergens may be considered as "true" sensitizers, in analogy to the definition of skin sensitization, and in contrast to respiratory irritants). In light of this, the European Center for Ecotoxicology and Toxicology of Chemicals convened a Task Force to evaluate the types of clinical methods and data sources and the implications of relying on such data for regulatory decision making from a scientific perspective.

Biomarkers.

Background: Fluid biomarkers provide a convenient way to predict AD pathophysiology. However, few studies have focused on determining associations with tau neurofibrillary tangle pathology in the early preclinical AD continuum, relevant to prevention strategies.

Methods: Ninety-nine cognitively unimpaired individuals from the ALFA+ cohort with valid F-RO-948 and F-flutemetamol PET, T1-weighted MRI, cognition, CSF, and plasma biomarkers were included.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Optimal Word Reading Rate as Evidenced by Frequency-tagging Electrophysiology.

Fast periodic visual stimulation (FPVS) coupled with EEG has been used for a decade to measure word-selective neural responses in (a)typical adults and developmental readers. Here, we used this FPVS-EEG approach to evaluate suitable and optimal stimulation frequency rates for prelexical and lexical word-selective responses and relate these rates to typical reading speed and interindividual variability in reading performance. EEG was recorded in 41 healthy adults who viewed words inserted periodically (1 Hz) at four different stimulation frequency rates (4 Hz, 6 Hz, 10 Hz, and 20 Hz).

Biomarkers.

Background: A novel method using diffusion-weighted imaging (DWI) allows for assessing microstructural injury in the gray matter by measuring cortical mean diffusivity (cMD). Previous studies have shown that altered cMD is related to amyloid (Aβ) cross-sectionally and can predict longitudinal cognitive decline and clinical progression, suggesting utility in clinical trials. However, the longitudinal associations between these measures are unknown.

Biomarkers.

Background: Alzheimer's Disease (AD) is a complex disorder and much of its etiopathology is still unknown. Here, we applied dimensionality reduction methods to disentangle cyptic patterns in CSF proteomic and lipidomic data.

Method: We studied 1121 CSF samples using targeted lipidomics based on liquid chromatography (LC)-MS/MS (mass spectrometry), generated by Lipometrix (Lueven, Belgium), and proteomic data generated by Somalogic (Boulder, Colorado) using the SOMAscan 7k Assay.

Biomarkers.

Background: Precision neuroscience is emerging as a transformative approach that aims to identify the right treatment for the right patient at the right time. To enable this, it is important to move beyond the categorization of patients based on clinical symptoms towards a biological definition of disease. For Alzheimer's disease, significant progress has been made in this direction, with the development of the "A/T/N" biomarker framework that classifies patients based on underlying pathophysiology.

Effective Management Strategies for Primary Lymphedema of the Lower Extremities: Integrating Conservative and Surgical Therapies in Early and Late Stages.

Introduction: Lymphedema, a debilitating characterized by localized fluid retention and tissue swelling, results from abnormalities in the lymphatic system. In the case of primary lymphedema, this condition is attributed to malformations in lymphatic vessels or nodes, and it is marked by a relentless progression leading to irreversible tissue fibrosis after repetitive inflammation. Many questions regarding its treatment, such as the choice of the type of intervention and the timing, still remain unanswered.

Public Health.

Background: Increasing evidence shows a link between arterial calcification in the heart-brain axis and cognitive performance. However, how calcification relates to acceleration of cognitive changes, and which specific cognitive domains are mostly affected, remains unclear. We assessed the impact of calcification in major arteries between the heart and brain on cognitive decline and focused on different cognitive domains.

Public Health.

Background: Despite evidence that sex can modulate Alzheimer's disease (AD) risk, whether risk factors are similarly related to AD markers in women and men remains largely unexplored. We aimed to assess how a combination of potentially modifiable risk factors are associated with cognitive and pathological markers of AD in older women and men.

Method: We included 135 cognitively unimpaired older adults (≥65 years old, 83 women; Table 1) from the Age-Well trial (NCT02977819; baseline data) with multidomain assessments of modifiable risk factors, including cardiovascular (body mass index, systolic blood pressure, LDL cholesterol), lifestyle (complex mental activity throughout life, physical activity, diet), and psychological (quality of life, depressive and anxiety symptoms, rumination, worry).

Biomarkers.

Background: The Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non-demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e.

Biomarkers.

Background: Recent developments in physiological and digital biomarkers provide an opportunity to shift the first diagnostic steps to the home-setting, thus allowing earlier detection and treatment of Alzheimer's disease (AD). Blood-based, magnetic resonance imaging, electrophysiological, digital and microbiome biomarkers have shown great promise and call for an evaluation of their accuracy, feasibility and safety in primary care and the community. The aim of PREDICTOM is to develop and test the accuracy of an artificial intelligence (AI) driven screening platform for the prediction and early detection of AD and to extend the clinical pathway to home-based screening using established and novel biomarkers.