Biomarkers.

Background: Accumulating evidence indicates that biological sex may influence clinical manifestation within the spectrum of frontotemporal lobar degeneration (FTLD), implying differences in cognitive reserve. Nonetheless, investigations into the impact of biological sex during the preclinical and minimally symptomatic stages of FTLD are lacking.

Method: We included 275 mutation carriers (158 females; 127 with C9orf72, 68 with GRN, and 80 with MAPT mutations) and 161 non-carrier familial controls (97 females) from the ALLFTD Consortium (Staffaroni et al.

Biomarkers.

Background: Individuals with Down Syndrome (DS) almost invariably develop Alzheimer's Disease (AD), but detecting early clinical changes is challenging due to comorbid intellectual disability, highlighting the importance of non-invasive biomarkers. Neuroimaging of the medial temporal lobe (MTL), a key site of tau pathology, shows promise as an early AD biomarker. Here, we aimed to characterise volumetric patterns of the MTL in DS across the AD clinical continuum, and define associations with AD cerebrospinal fluid (CSF) biomarkers.

Biomarkers.

Background: Alzheimer´s disease (AD) is the main cause of death in adults with Down syndrome (DS). We describe the unique contributions of the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort by studying longitudinal changes in plasma and cerebrospinal fluid (CSF) markers.

Method: We included DABNI participants with DS that contributed at least two plasma and/or CSF samples and were asymptomatic (aDS, n=155), had prodromal AD (pDS, n=46) or had AD dementia (dDS; n=53) at baseline, together with 172 euploid cognitively normal controls (CN).

Biomarkers.

Background: To date, limited data exist concerning the utility of FDG-PET in detecting Alzheimer's Disease (AD) in Down Syndrome (DS). Yet, sensitive biomarkers for neurodegeneration are essential in this population genetically predisposed for AD. Therefore, we aimed at characterizing the effect of age, disease stage and AD pathology on brain metabolism in a large cohort of adults with DS.

Biomarkers.

Background: Primary progressive aphasia (PPA) is a language-based dementia linked with underlying Alzheimer's disease (AD) or frontotemporal dementia. Clinicians often report difficulty differentiating between the logopenic (lv) and nonfluent/agrammatic (nfv) subtypes, as both variants present with disruptions to "fluency" yet for different underlying reasons. In English, acoustic and linguistic markers from connected speech samples have shown promise in machine learning (ML)-based differentiation of nfv from lv.

Public Health.

Background: The extended life expectancy in individuals with Down Syndrome (DS) has led to the emergence of age-related diseases, with Alzheimer's disease (AD) being particularly noteworthy due to its nearly full penetrance. The level of intellectual disability (ID), regarded as a proxy for cognitive reserve (CR), explains heterogeneity in cognitive and functional abilities. Despite this, there is a notable lack of exploration into the characterization of resilience factors and their potential influence on the progression along the AD continuum in this population.

Biomarkers.

Background: The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut-points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability.

Biomarkers.

Background: Prediction of progression to Alzheimer's Disease Dementia (ADD) at the Mild Cognitive Impairment (MCI) stage is an unmet medical need. Mitochondrial dysfunction in Alzheimer's Disease at the brain and systemic level has been extensively described. Our previous studies showed an altered mtDNA methylation pattern throughout AD progression in human postmortem brains (Blanch et al.

Developing Topics.

Background: Synapse loss represents the closest correlate of cognitive decline in Alzheimer's Disease (AD). Standard microscopy, due to increased diffraction of light with tissue depth, imposes a limit on axial resolution extending to ∼ 700nm. Array tomography (AT), developed by Micheva & Smith (2007), extends this axial limit via physical sectioning of resin-embedded tissue into ribbons of 70nm contiguous sections that are serially imaged and reconstructed into 3D volumes; thus, allowing for nanometric synaptic puncta to be resolved at the mesoscale.

Alzheimer's Imaging Consortium.

Background: Individuals with Down Syndrome (DS) almost invariably develop Alzheimer's Disease (AD), but detecting early clinical changes is challenging due to comorbid intellectual disability, highlighting the importance of non-invasive biomarkers. Neuroimaging of the medial temporal lobe (MTL), a key site of tau pathology, shows promise as an early AD biomarker. Here, we aimed to characterise volumetric patterns of the MTL in DS across the AD clinical continuum, and define associations with AD cerebrospinal fluid (CSF) biomarkers.

Technology and Dementia Preconference.

Background: Primary progressive aphasia (PPA) is a language-based dementia linked with underlying Alzheimer's disease (AD) or frontotemporal dementia. Clinicians often report difficulty differentiating between the logopenic (lv) and nonfluent/agrammatic (nfv) subtypes, as both variants present with disruptions to "fluency" yet for different underlying reasons. In English, acoustic and linguistic markers from connected speech samples have shown promise in machine learning (ML)-based differentiation of nfv from lv.

The immunological landscape of primary biliary cholangitis: Mechanisms and therapeutic prospects.

Primary Biliary Cholangitis (PBC) is a chronic cholestatic liver disease characterized by the progressive destruction of intrahepatic bile ducts, leading to fibrosis, and potentially cirrhosis. PBC has been considered a prototypical autoimmune condition, given the presence of specific autoantibodies and the immune response against well-defined mitochondrial autoantigens. Further evidence supports the interaction of immunogenetic and environmental factors in the aetiology of PBC.

Dissociating language switching from executive control in bilinguals with MCI.

Bilingual language control is a dynamic cognitive system that enables individuals to effectively manage language use and prevent interference when switching between languages. Research indicates that certain neurodegenerative conditions may influence language-switching abilities or hinder the suppression of cross-language interference. However, it remains uncertain whether neurodegeneration primarily affecting mesial temporal structures, such as Mild Cognitive Impairment (MCI), impacts lexical retrieval in dual-language naming conditions.

Impaired Cerebrospinal Fluid Lipoprotein-Mediated Cholesterol Delivery to Neurons in Alzheimer's Disease.

In the central nervous system, apolipoprotein (APO) E-containing high-density lipoprotein (HDL)-like particles mediate the transport of glial-derived cholesterol to neurons, which is essential for neuronal membrane remodeling and maintenance of the myelin sheath. Despite this, the role of HDL-like cholesterol trafficking on Alzheimer's disease (AD) pathogenesis remains poorly understood. We aimed to examine cholesterol transport via HDL-like particles in cerebrospinal fluid (CSF) of AD patients compared to control individuals.

Posterior Cortical Atrophy Due to Alzheimer Disease in a Person With Down Syndrome: A Case Report.

Objectives: Atypical variants are rare in genetically determined Alzheimer disease (AD). This case describes a patient with Down syndrome-associated Alzheimer disease (DSAD) who presented with symptoms of posterior cortical atrophy (PCA).

Methods: We conducted a clinical and cognitive evaluation, genotyping, determination of AD biomarkers in CSF, structural MRI, [18F]FDG-PET, and tau-PET ([18F]PI2620) scans.

Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic.

Background: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic.

Glucagon-like peptide-1 receptor agonists and risk of gastrointestinal cancers: A systematic review and meta-analysis of randomized controlled trials.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used for glucose lowering and weight-loss. However, their association with gastrointestinal cancer remains uncertain. This meta-analysis assesses the risk of gastrointestinal cancer in patients treated with GLP-1 RAs.

Large-scale CSF proteome profiling identifies biomarkers for accurate diagnosis of Frontotemporal Dementia.

Diagnosis of Frontotemporal dementia (FTD) and the specific underlying neuropathologies (frontotemporal lobar degeneration; FTLD- Tau and FTLD-TDP) is challenging, and thus fluid biomarkers are needed to improve diagnostic accuracy. We used proximity extension assays to analyze 665 proteins in cerebrospinal fluid (CSF) samples from a multicenter cohort including patients with FTD (n = 189), Alzheimer's Disease dementia (AD; n = 232), and cognitively unimpaired individuals (n = 196). In a subset, FTLD neuropathology was determined based on phenotype or genotype (FTLD-Tau = 87 and FTLD-TDP = 68).