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.

Biomarkers.

Background: Amyloid-β (Aβ) pathology affects resting state functional connectivity (RSFC), even in cognitively unimpaired (CU) individuals. However, the impact of such an aberrant RSFC on cognitive decline is yet to be determined. Moreover, most prior research focused on fibrillary Aβ deposition to predict RSFC, while early Aβ dysmetabolism as reflected by cerebrospinal fluid (CSF) concentrations has received less attention.

Biomarkers.

Background: Sleep-wake alterations are common symptoms in Alzheimer's Disease (AD) associated with faster cognitive decline. Noradrenaline dysfunction and neuroinflammation have been proposed as potential driving mechanisms. The ADIS project aims to study the relationship between sleep-wake patterns, immune signatures (peripheral blood cytotoxic lymphocytes), and noradrenergic markers across the AD spectrum.

Biomarkers.

Background: Obstructive sleep apnoea (OSA) is the sleep disorder most frequently found in patients with Alzheimer's disease (AD). The intermittent hypoxia (IH) caused by OSA may participate in AD pathogenesis through increase in oxidative damage and inflammation. We aimed to identify inflammatory and redox genes differentially expressed in the blood from AD patients with severe OSA compared with those with nonsevere OSA.

Biomarkers.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and the leading cause of dementia in the elderly. New approaches to study AD are still needed to identify and validate blood-based diagnostic biomarkers that could be useful for its early diagnosis. Circulating autoantibodies (AAbs) and their target proteins (autoantigens) are promising candidate biomarkers to aid in AD early diagnosis.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by early changes in brain structure and cognitive function before the age of onset. This study investigated whether the genetic load for clinical AD and AD pathology predicts AD-related brain and cognitive changes over a 3-year period, targeting the preclinical phase in cognitively unimpaired (CU) middle-aged individuals.

Method: The sample of the study was defined by 429 CU middle-aged participants at risk of AD from the ALFA+ nested cohort with available information on genetics, brain imaging markers and cognitive data [Table 1].

Biomarkers.

Background: Synaptic loss is an eminent feature of tauopathies. The recently developed novel SV2A PET-tracer UCB-J has shown great promise in tracking synaptic loss in tauopathies. However, there have been discrepancies between the in vivo findings and a lack of mechanistic insight.

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.

Biomarkers.

Background: Glial fibrillary acidic protein (GFAP) is a marker of cerebral astrogliosis and occasionally elevated in patients with dementia. GFAP in cerebrospinal fluid (CSF), is routinely requested in referrals to neurochemistry laboratories; however, its ability to differentiate dementias and diagnostic capability is unclear. Our aim was to elucidate this, using two large datasets.

Biomarkers.

Background: KLOTHO-VS heterozygosity (KL-VS) has been posited to be a protective factor against age-related disease and cognitive decline, having been associated with increased cortical volumes and brain connectivity, as well as improved cognition in healthy elderly individuals. Conversely, the APOE-ε4 allele is a primary risk factor for the development of Alzheimer's disease (AD), with ε4 carriers more likely to have greater β-amyloid burden, earlier age of AD onset, and accelerated rates of cognitive decline. Relatively few studies have investigated the interaction between these two genetic factors, with those that have presenting conflicting findings.

Biomarkers.

Background: Mild cognitive impairment (MCI), is characterized by cognitive dysfunction not severe enough to affect one's activities of daily living (ADLs)1. Annually, approximately 15-20% adults 65 and older will present with MCI 1. MCI is considered a significant risk factor and a robust predictor for developing dementia.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Biomarkers.

Background: Brain atrophy is a normal part of healthy aging, but it is aggravated by several neurodegenerative diseases. Previous studies have described a large heterogeneity in individual neurodegeneration patterns, but the underlying brain mechanisms are currently not fully understood. From a graph theory-based framework, the estimation of subject-specific focal or multifocal brain atrophy in healthy aging and in the preclinical stage of different neurodegenerative diseases, such as Alzheimer's disease (AD), will help to better understand individual atrophy networks and likely improve prediction of phenotypic heterogeneity in disease trajectories.

Should CAR-T cell therapy be considered a standard of care for patients with refractory diffuse large B-cell lymphoma in second line treatment?

Introduction: CAR-T therapy has transformed the treatment landscape for relapsed/refractory diffuse large B-cell lymphomas (DLBCL).

Areas Covered: This article reviews the existing evidence for using CAR-T therapy as a second-line treatment. Two major phase 3 trials, ZUMA-7 and TRANSFORM, have shown that axi-cel and liso-cel, respectively, offer superior outcomes compared to historical standard chemoimmunotherapy and consolidation with autologous hematopoietic stem cell transplantation (auto-HCT).

Role of a Whole Plant Foods Diet in Breast Cancer Prevention and Survival.

Breast cancer (BC) is one of the leading causes of death and morbidity among women worldwide. Epidemiologic evidence shows that the risk of BC and other chronic diseases decreases as the proportion of whole plant foods increases, while the proportion of animal foods (fish, meat, poultry, eggs, seafood, and dairy products) and non-whole plant foods (e.g.

Biomarkers.

Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.

Biomarkers.

Background: Recent studies in brain functional connectivity (FC) have shifted focus to dynamic functional connectivity (dFC), exploring transient aspects of FC over time. This shift is particularly relevant for Alzheimer's Disease (AD), as it involves altered cognition-supporting networks. Our study aims to characterize the evolution of dFC across the entire pre-dementia AD spectrum using Amplitude Envelope Correlation (AEC) recurrence matrices and to link this to cognitive decline.

Biomarkers.

Background: The emergence of disease-modifying drug therapies is expected to revolutionize the field of Alzheimer's disease (AD). Recent results from anti-amyloid clinical trials highlight the importance of early identification and accurate risk-stratification of individuals in early stages of the disease. In this context, the Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Prognostic and Natural History Study (PNHS) was established, leveraging existing cohorts to alleviate the burden of recruiting de novo participants.

Biomarkers.

Background: CSF t-tau is considered a marker of neuronal injury in AD and strongly correlates with cognitive impairment. Evidence suggests that women accumulate more tau pathology early in AD than men. However, how pregnancy influences this relationship is unclear.

Biomarkers.

Background: Leukocyte telomere length (LTL) serves as a proxy for tissue-specific TL and peripheral immune aging. Its association with aging-related brain endophenotypes, cognitive functioning, and Alzheimer's disease (AD) risk is established, but the underlying molecular mechanisms remain elusive. Investigating LTL's association with AD biomarkers is crucial for identifying its role in brain resilience and disease progression.

Biomarkers.

Background: Glial fibrillary acidic protein (GFAP) is an astrocytic cytoskeletal protein and a promising blood biomarker for Alzheimer's disease (AD) and other neurodegenerative diseases. To date, the genetic architecture of plasma GFAP has not been characterized. We conducted a multi-ancestry meta-analyses of genome-wide association studies (GWAS) in diverse population-based cohorts to identify genetic variants associated with plasma levels of GFAP and to investigate their implication for neurological diseases.

Biomarkers.

Background: Blood-based biomarkers offer a non-invasive and cost-effective means for Alzheimer's disease (AD) detection. In this study, we performed a direct comparison of these novel biomarkers in a memory clinic population to facilitate their implementation into clinical practice.

Method: We included a total of 208 patients with cognitive complaints from the BIODEGMAR cohort at Hospital del Mar (Barcelona, Spain).

Biomarkers.

Background: Glial fibrillary acidic protein (GFAP) is a putative blood biomarker for Alzheimer's disease (AD). Most studies measure plasma GFAP (pGFAP) utilizing the Single Molecule Array (Simoa) platform or other high-cost platforms. However, we aim to validate the value of GFAP as a blood biomarker for AD using chemiluminescent microparticle immunoassay (CMIA), an ubiquitous lower-cost platform.