Aminoalkylation of Alkenes Enabled by Triple Radical Sorting.

The direct synthesis of C(sp)-rich architectures is a driving force for innovation in synthetic organic chemistry. Such scaffolds impart beneficial properties onto drug molecules that correlate with greater clinical success. Consequently, there is a strong impetus to develop new methods by which to access sp-rich molecules from commercial feedstocks, such as alkenes.

Response of Amblyseius swirskii to deltamethrin.

Background: The rising demand for environmentally friendly pest control highlights the importance of understanding the interaction between natural enemies and pesticides. Amblyseius swirskii, a predatory mite extensively used in biocontrol, plays a crucial role in managing pest populations in agricultural systems. Integrating this mite with selective pesticide use within integrated pest management (IPM) would significantly advance pest control and may reduce pesticide residues in the environment and agricultural produce.

Biomarkers.

Background: biomarkers are essential in order to make a diagnosis with a high level of accuracy in patients with cognitive and behavior complaints. However, molecular imaging biomarkers not always provide an answer in daily clinical practice.

Methods: retrospective and descriptive study in patients with Amyloid PET (APscans) implemented according to rational use of this technic, between January 2019-November 2023 in Neurology Department, Infanta Leonor Hospital, Madrid, Spain.

Biomarkers.

Background: Alzheimer's Disease (AD) is associated with sleep disturbances. Moreover, individuals with sleep disturbances have been reported to have a higher risk for developing AD. The measurement of sleep behavior therefore opens the opportunity for a potential digital biomarker of AD.

Biomarkers.

Background: Neurofilament light chain (NfL) is a fluid biomarker of axonal damage reported to be elevated in cases with dementia, and particularly in FTD. In this study we evaluate the performance of a recently developed NfL assay to be analyzed through the Lumipulse chemiluminescent platform, which is frequently available in clinical settings for the study of AD core biomarkers.

Method: We evaluated CSF NfL levels using the Lumipulse G600II platform (Fujirebio, Iberia) in 70 cases, including 33 patients with AD (supported by CSF biomarkers consistent with an A+T+(N)+ classification scheme), 26 with confirmed FTD (typical phenotype and CSF with a A-T- profile), and 11 controls.

Biomarkers.

Background: The Centiloid method (CL) was introduced as a tracer-independent measure for cortical amyloid load and is now commonly used in Alzheimer's disease (AD) clinical trials. To facilitate its implementation into clinical settings, the AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations of the Centiloid scale, which has been submitted to the European Medicine Agency for endorsement as a Biomarker Qualification Opinion.

Method: Screening of the literature was performed on the 7/11/23 on PubMed to identify articles mentioning "Centiloid".

Biomarkers.

Background: Alzheimer's Disease (AD) has a long preclinical stage, in which brain metabolic alterations precede the symptoms onset. Therefore, an early and proper diagnosis of AD is essential for prevention and therapeutic evaluation. Current diagnosis and staging procedures rely on neuroimaging techniques, such as positron emission tomography (PET), which require intensity normalization to ensure the correct interpretation of the data.

Biomarkers.

Background: A key neuropathological feature in the early stages of Alzheimer's disease (AD) involves hippocampal dysfunction arising from the accumulation of amyloid-β (Aβ). Previously, our laboratory identified a shift in the synaptic plasticity long term potentiation (LTP)/long term depression (LTD) induction threshold, leading to memory deficits in a non-transgenic murine model of early AD generated by intracerebroventricular (icv.) injections Aβ oligomers (oAβ), one of the most predominant pathogenetic factors in initial stages of the disease.

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common neuropathologic finding at advanced age that associates with hippocampal sclerosis (HS) and is often comorbid with AD pathology. Neuroimaging measurements of LATE-NC-associated limbic degeneration have been proposed as indirect biomarkers, but molecular-specific biomarkers for LATE-NC are still lacking. Here we used combined ante-mortem blood and MRI data to study TDP-43 levels in plasma-derived small extracellular vesicles (sEV-TDP-43) and hippocampal volume (HV) in relation to LATE-NC and HS at autopsy.

Biomarkers.

Background: Beyond dementia syndromes, cognitive symptoms are highly prevalent in Parkinson's disease (PD), often manifesting as mild cognitive impairment (MCI). Yet, their detection and characterization remain suboptimal because standard approaches rely on subjective impressions derived from lengthy, univariate tests. Here we introduce a novel approach to detect cognitive symptom severity and identify MCI in PD using fully automated word property analyses on brief verbal fluency tasks.

Biomarkers.

Background: Understanding the genetic etiology of Alzheimer's disease (AD) has been a major focus of research in neurodegenerative diseases. Amid the three common allelic variants of the apolipoprotein E (APOE) gene in humans, called APOE ε2, ε3 and ε4, the ε4 allele is the most common genetic risk factor for late-onset AD, being found in 20% of the world population.

Method: We used Event-Related Potentials (ERP) and Event-Related Spectral Perturbation (ERSP) as features for classification of apolipoprotein E ϵ4 (APOE ε4) allele carriers in AD patients and healthy controls.

Biomarkers.

Background: Detecting Alzheimer's disease (AD) biological hallmarks before clinical symptoms emerge is now possible with available blood-based biomarkers. However, the rate of cognitive decline varies among individuals at risk of AD, and accurate prognostic blood-based biomarkers are lacking. Our goal is to identify plasma proteins predictive of fast cognitive decline in asymptomatic individuals at risk of AD.

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: Recent reports support the use of plasma biomarkers of neurodegeneration and neuroinflammation, as determined through ultrasensitive single molecular arrays (SIMOA), to screen and diagnose patients with dementia. However, their translation to clinical settings requires further studies.

Methods: We evaluated plasma samples from 186 individuals including 72 patients with AD (supported by CSF biomarkers consistent with an A+T+N+ classification scheme), 44 with confirmed FTD, 48 cognitively intact nonagenarians, and 22 controls (ages 40-83 years).

Biomarkers.

Background: Changes in Amyloid-β (A) and hyperphosphorylated Tau (T) in the brain and cerebrospinal fluid (CSF) precedes AD symptoms, making the CSF proteome a potential avenue to understand disease pathophysiology and facilitate reliable diagnostics and therapies.

Method: We used the Somascan assay for measuring the protein levels of 7,029 analytes in CSF of 2,286 participants from four different cohorts. We employed a three-stage analytical approach (discovery, replication, and meta-analysis).

Biomarkers.

Background: The exact mechanism underlying amyloid-related imaging abnormalities (ARIA) is unknown. Several factors explain ARIA risk, including the presence of microbleeds, APOE4 carriership, and very low Aβ42 levels. The cerebrospinal fluid (CSF) proteome reflects ongoing mechanisms and, thereby, provides an accessible fluid to refine risk of ARIA development.

Hospital burden of pneumococcal disease in Spain (2016-2022): A retrospective study.

Pneumococcal disease is a leading cause of morbidity and mortality worldwide. From 2016 to 2022, 358,603 hospitalized patients were identified as having pneumococcal disease. The overall annual hospitalization rate was 108.

Biomarkers.

Background: About 20-30% of clinically diagnosed AD dementia patients do not meet pathologic criteria for AD and this proportion is even higher in amnestic MCI. Among tau-negative amnestic patients, limbic-predominant age-related TDP-43 encephalopathy (LATE) has been described as a principal diagnostic alternative, especially at advanced age. LATE is characterized by a specific temporo-limbic hypometabolic signature on FDG-PET that may aid in differential diagnosis.

Biomarkers.

Background: The preclinical stage of Alzheimer's disease (AD) has gained attention for the window of opportunity it opens for early detection and intervention. Given the high invasiveness of PET and CSF markers, electrophysiology and plasma biomarkers are being studied as alternate biomarkers for early detection and disease tracking. The aim of this study is twofold.

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: Brain, cerebrospinal fluid (CSF), and plasma metabolomics have been informative in identifying disrupted metabolism pathways in Alzheimer's disease (AD). However, many AD-focused metabolomics studies profiled a relatively small number of individuals and metabolites, especially for CSF. In addition, past studies were limited to one or two tissues.

Biomarkers.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

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: Sleep disturbances have been identified as a risk factor for developing dementia. The hypothalamus is involved in sleep regulation and may be affected early by neurodegeneration. Our aim was to investigate the relationship between subjective sleep and hypothalamic structure in adults at higher risk of developing dementia.

Biomarkers.

Background: The brain undergoes structural changes during aging, such as gray matter loss, enlarged ventricles, and sulcal widening. However, previous studies have primarily investigated these changes in isolation, without describing the complex spatial relationships between overall brain shape and regions. Here, we tested how gradients of expansion and compression of the global shape of the brain as well as between homologous brain regions across hemispheres are affected by age, and whether these changes further contribute to clinical impairment and cognitive deficits in older adults.