Let 'Pregnant Women Choose the Destiny for Themselves and Their Child'. How Fertility Clinic Digital Platforms Frame Preimplantation Genetic Testing (PGT) in Spain.

Preimplantation Genetic Testing (PGT) is used to select in vitro embryos for distinct clinical contexts and purposes. PGT for monogenic conditions (PGT-M), also known as Preimplantation Genetic Diagnosis (PGD), enables the prevention of passing on a known genetic disorder to one's offspring. Conversely, PGT for aneuploidies (PGT-A), or Preimplantation Genetic Screening (PGS), is used to improve IVF success rates in fertility patients and increase confidence about the health outcomes of potential offspring.

Biomarkers.

Background: The driving mechanisms of structural brain alterations in the earliest stages of Alzheimer's disease (AD) are not well understood. Previous heterogeneous findings in preclinical AD, including subtle atrophy and also increased grey matter (GM) volume, underscore the need for further exploration. This study uses an extensive fluid biomarkers panel to identify pathological drivers behind longitudinal GM changes in cognitively unimpaired (CU) adults.

Biomarkers.

Background: Nearly all people with Down Syndrome (DS) develop Alzheimer's dementia (AD) by the 7 decade of life. However, whether the alterations in fluid biomarker levels associated with DS follow the same pattern to those observed in other forms of AD is not well understood.

Method: We used mass spectrometry-based proteomics to measure 1116 proteins in cerebrospinal fluid (CSF) across euploid controls (n=130), sporadic late-onset AD (LOAD, n=89), asymptomatic DS (n=117), prodromal DS (n=57), and dementia DS (n=80) cases, and compared the protein changes observed in DS to those in LOAD and to those recently described in autosomal dominant AD (ADAD).

Biomarkers.

Background: Cognitive Reserve (CR) refers to the brain's ability to maintain optimal cognitive function despite damage or pathology. The neural implementation of CR is a major research focus, and resting-state functional connectivity (RSFC) has emerged as a promising imaging correlate of CR. We assessed RSFC as a function of two different proxy measures of CR and further assessed the impact of these brain networks on longitudinal cognitive performance in a sample of cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD).

Biomarkers.

Background: Alzheimer disease (AD) related cognitive decline occurs at relatively young ages in individuals with Down syndrome (DS, early-mid 50s) and in those with autosomal dominant mutations (ADAD, 40-50s). Both groups show similar patterns of amyloid accumulation. We examined if brain volumes are similarly affected by AD pathology in individuals with DS and ADAD.

Biomarkers.

Background: Cognitive resilience can be defined as better-than-expected cognitive performance in the context of Alzheimer's disease (AD) pathologies or increased AD risk. We investigated pathways associated with cognitive resilience trajectories in amyloid positive (A+) and/or APOE4 cognitively unimpaired (CU) older adults including brain resilience, resistance to AD pathologies and vascular pathology.

Method: We included 534 CU ADNI participants with available cognitive data, longitudinal amyloid-PET ( [F]florbetaben and [F]florbetapir) and structural MRI (gray matter volumes) and, as ubset with tau-PET ( [F]AV1451) (n = 287) and white matter hyperintensities (n = 467) volume data (n = 534).

Biomarkers.

Background: While Lewy body (LB) pathology typically associates with a distinct clinical profile compared to Alzheimer's disease (AD), early memory deficits are not uncommon and can confound clinical diagnosis of amnestic patients. Moreover, approximately 30-60% of AD patients have concomitant LB pathology, which has been reported to affect the clinical phenotype and result in a more aggressive disease course. Recently developed α-synuclein seed amplification assays (αSyn-SAAs) have demonstrated high diagnostic accuracy for LB diseases, but the role of these novel biomarkers in the context of amnestic presentations typical for AD remains to be investigated in more detail.

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: Tau pathology and neurodegeneration in the medial temporal lobe (MTL) are highly associated in Alzheimer's Disease (AD). However, the spatial pattern of neurodegeneration, contribution of individual tau inclusion types, and influence of MTL co-pathologies (i.e.

Biomarkers.

Background: Cardiovascular disease and dementia often co-exist at advanced stages. Yet, midlife longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health are scarce. We aimed to determine the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis and cardiovascular risk factors in middle-aged asymptomatic individuals.

Biomarkers.

Background: Lamin A is barely expressed in human brain neurons or in murine models such as mice and rats. However, in Alheimer´s disease (AD) brains, neurons in the hippocampus and entorhinal cortex abnormally express lamina A from the initial stages of the disease, being a biomarker together with phosphorylated Tau of the nuclear pathology of AD. Constipation and mesenteric neuronal loss are related to aging and neurodegenerative diseases such as AD.

Biomarkers.

Background: Recent results from clinical trials in Alzheimer's disease (AD) emphasize the importance of treating early-stage disease. However, recruitment of preclinical AD participants is difficult due to the lack of symptoms, and the costs and/or invasiveness of established CSF and PET tests. We aimed to investigate whether plasma p-tau217 could be used to pre-screen cognitively unimpaired (CU) potential participants for amyloid-β (Aβ) pathology to improve the efficiency of clinical trial recruitment.

Biomarkers.

Background: Co-morbid Alzheimer's disease (AD) pathology is a major risk factor for cognitive impairment (CI) in PD, but whether and how AD co-pathology affects the clinical phenotype of PD-CI is incompletely understood. Recently validated plasma biomarkers for AD pathology, such as ptau217, hold great promise to revolutionize the diagnosis of neurodegenerative diseases. Here, we used plasma ptau217 to detect AD co-pathology in a well-characterized cohort of PD patients with CI and examine its associations with APOE4 genotype, cognitive profile, and cerebral hypometabolism on FDG-PET.

Biomarkers.

Background: Investigating age-related changes in MEG brain networks offers significant potential for comprehending aging trajectories and unveiling anomalous patterns associated with neurodegenerative disorders, such as Alzheimer's disease. In this study, we extended a deep learning model called Fully Hyperbolic Neural Network (FHNN) to embed MEG brain connectivity graphs into a Lorentz Hyperboloid model for hyperbolic space. Through these embeddings, we then explored the impact of aging on brain functional connectivity across multiple decades.

Biomarkers.

Background: Alzheimer's disease (AD) is a devastating neurodegenerative disease with delayed diagnosis until the manifestation of symptoms. Although the emergence of blood-based biomarkers offers hope for easy detection of AD, existing AD-associated blood biomarkers, known as the "blood ATN biomarkers", mainly capture the pathological hallmarks of AD, overlooking other AD-associated biological processes such as inflammation and vascular dysfunctions. Therefore, developing a blood-based biomarker assay that captures dysregulation beyond the ATN biomarkers may help advance early detection and staging of AD, enabling a comprehensive examination of the disease status METHOD: We leveraged ultrasensitive proteomic technology to develop a blood-based, multiplex biomarker assay for AD.

Biomarkers.

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 having the greatest utility. Increased and simplified access to blood biomarkers is crucial for early diagnosis, proper patient management and prompt initiation of disease-modifying treatments. The DROP-AD project investigates the capability of finger-prick collection to accurately measure p-tau217, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

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: The detrimental effects of air pollution on health are well-documented, yet its impact on brain structure in the early asymptomatic stages of Alzheimer's disease (AD) remains under-explored. This study investigated the relationship between air pollution and brain imaging features, focusing on the moderating role of genetic factors associated with AD and inflammation.

Methods: A total of 1,153 individuals from the ALFA cohort, many within the Alzheimer's continuum, with available genotyping, air pollution estimation and magnetic resonance imaging were included (62.

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: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

Biomarkers.

Background: In murine models, peripheral blood factors have been identified as having either a brain rejuvenating or ageing effect. However, it is unclear whether these blood factors have similar effects in humans. We aimed at testing the association between these blood factors and cognitive performance in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD).

Biomarkers.

Background: Blood biomarkers are essential in identifying Alzheimer's disease (AD) pathology. To ensure their clinical use, it is crucial to understand pre-analytical factors such as fasting conditions and long-term storage at -80°C. This study evaluates the effect of these factors on plasma biomarker concentrations for detecting AD pathology and neurodegeneration.

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.

Biomarkers.

Background: Alzheimer's disease (AD) features a complex interplay of factors influencing cognitive decline. While CSF and plasma biomarkers have widely demonstrated their diagnostic utility, whether they may add prognostic value remains unrevealed. With this longitudinal study we aim to address this knowledge gap by evaluating the predictive value of several fluid biomarkers over cognitive decline in a cohort of biomarker-confirmed AD individuals.

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.