Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells.

The H3K79 methyltransferase DOT1L is essential for multiple aspects of mammalian development where it has been shown to regulate gene expression. Here, by producing and integrating epigenomic and spike-in RNA-seq data, we decipher the molecular role of DOT1L during mouse spermatogenesis and show that it has opposite effects on gene expression depending on chromatin environment. On one hand, DOT1L represses autosomal genes that are devoid of H3K79me2 at their bodies and located in H3K27me3-rich/H3K27ac-poor environments.

Effects of blood-brain barrier opening using ultrasound on tauopathies: A systematic review.

Unlabelled: Blood-brain barrier opening with ultrasound can potentiate drug efficacy in the treatment of brain pathologies and also provides therapeutic effects on its own. It is an innovative tool to transiently, repeatedly and safely open the barrier, with studies showing beneficial effects in both preclinical models for Alzheimer's disease and recent clinical studies. The first preclinical and clinical work has mainly shown a decrease in amyloid burden in mice models and in patients.

Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

A PARK7 Mutation-Induced Early-Onset Parkinson's Disease in a Moroccan Family: Expanding the Geographic Spectrum.

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms, with a significant genetic component. Early-onset Parkinson's disease (EOPD), manifesting before age 45, is often linked to mutations in genes such as PARK2, PINK1, and PARK7, the latter coding for the protein DJ-1.

Objective: We present the first reported cases of EOPD carrying a previously undescribed homozygous PARK7 mutation, p.

Identify biological Alzheimer's disease using a novel nucleic acid-linked protein immunoassay.

Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

Polygenic risk scores for atrial fibrillation and heart failure and the risk of stroke and dementia.

Atrial fibrillation and heart failure have both been suggested to increase stroke and dementia risk. However, in observational studies, reversed causation and unmeasured confounding may occur. To mitigate these issues, this study aims to investigate if higher genetic risk for atrial fibrillation and heart failure increases dementia and stroke risk.

Short-term variability of Alzheimer's disease plasma biomarkers in a mixed memory clinic cohort.

Background: For clinical implementation of Alzheimer's disease (AD) blood-based biomarkers (BBMs), knowledge of short-term variability, is crucial to ensure safe and correct biomarker interpretation, i.e., to capture changes or treatment effects that lie beyond that of expected short-term variability and considered clinically relevant.

MAPPING THE CEREBROSPINAL FLUID PROTEOME IN BIPOLAR DISORDER.

Background: Bipolar disorder (BD) is a severe psychiatric condition with unclear etiology and no established biomarkers. Here, we aimed to characterize the cerebrospinal fluid (CSF) proteome in euthymic BD individuals to identify potential protein biomarkers.

Methods: We employed nano-flow liquid chromatography coupled to high-resolution mass spectrometry to quantify over 2,000 CSF proteins in 374 individuals from two independent clinical cohorts (n=164+89 and 66+55 cases and controls, respectively).

Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment.

Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases primarily affecting motor neurons. Among these, spastic paraplegia type 11 (SPG11) represents a complex form of HSP caused by deleterious variants in the SPG11 gene, which encodes the spatacsin protein. Previous studies have described several potential roles for spatacsin, including its involvement in lysosome and autophagy mechanisms, neuronal and neurites development or mitochondria function.

Novel synaptic markers predict early tau pathology and cognitive deficit in an asymptomatic population at risk of Alzheimer's disease.

Cognitive dysfunction in Alzheimer's disease (AD) correlates closely with pathology in the neuronal microtubule-associated protein tau. Tau pathology may spread via neural synapses. In a population of cognitively unimpaired elderly at elevated risk of AD, we investigated four cerebrospinal (CSF) markers of synaptic dysfunction and degeneration.

Contribution of neuroimaging to the understanding of social cognition in epilepsy.

This narrative review aims to identify and summarize existing research to better understand the pathophysiological and neuroanatomical bases of social cognition deficits in people with epilepsy. The neuroanatomical basis of social cognition was primarily examined in healthy subjects. In healthy individuals, social cognition is supported by a complex network of interconnected brain regions.

New onset refractory status epilepticus: Long-term outcomes beyond seizures.

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps.

Association between herpes simplex virus infection and Alzheimer's disease biomarkers: analysis within the MAPT trial.

In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer's disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan.

Plasma biomarkers of amyloid, tau, astrogliosis, and axonal injury in a mixed memory clinic cohort.

Introduction: Studies have shown that blood biomarkers can differentiate dementia disorders. However, the diagnosis of dementia still relies primarily on cerebrospinal fluid and imaging modalities. The new disease-modifying treatments call for more widely applicable biomarkers.

Plasma N-terminal tau fragment is an amyloid-dependent biomarker in Alzheimer's disease.

Introduction: Novel fluid biomarkers for tracking neurodegeneration specific to Alzheimer's disease (AD) are greatly needed.

Methods: Using two independent well-characterized cohorts (n = 881 in total), we investigated the group differences in plasma N-terminal tau (NT1-tau) fragments across different AD stages and their association with cross-sectional and longitudinal amyloid beta (Aβ) plaques, tau tangles, brain atrophy, and cognitive decline.

Results: Plasma NT1-tau significantly increased in symptomatic AD and displayed positive associations with Aβ PET (positron emission tomography) and tau PET.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Age-Trajectories of Higher-Order Diffusion Properties of Major Brain Metabolites in Cerebral and Cerebellar Gray Matter Using In Vivo Diffusion-Weighted MR Spectroscopy at 3T.

Healthy brain aging involves changes in both brain structure and function, including alterations in cellular composition and microstructure across brain regions. Unlike diffusion-weighted MRI (dMRI), diffusion-weighted MR spectroscopy (dMRS) can assess cell-type specific microstructural changes, providing indirect information on both cell composition and microstructure through the quantification and interpretation of metabolites' diffusion properties. This work investigates age-related changes in the higher-order diffusion properties of total N-Acetyl-aspartate (neuronal biomarker), total choline (glial biomarker), and total creatine (both neuronal and glial biomarker) beyond the classical apparent diffusion coefficient in cerebral and cerebellar gray matter of healthy human brain.

Robust and time-resolved estimation of cardiac sympathetic and parasympathetic indices.

The time-resolved analysis of heart rate (HR) and heart rate variability (HRV) is crucial for the evaluation of the dynamic changes of autonomic activity under different clinical and behavioural conditions. Standard HRV analysis is performed in the frequency domain because the sympathetic activations tend to increase low-frequency HRV oscillations, while the parasympathetic ones increase high-frequency HRV oscillations. However, a strict separation of HRV into frequency bands may cause biased estimations, especially in the low-frequency range.

Manganese overload as a co-factor of neurological symptoms in a patient with sclerosing cholangitis due to Langerhans cell histiocytosis.

Not available.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Linking heartbeats with the cortical network dynamics involved in self-social touch distinction.

Research on interoception has revealed the role of heartbeats in shaping our perceptual awareness and embodying a first-person perspective. These heartbeat dynamics exhibit distinct responses to various types of touch. We advanced that those dynamics are directly associated to the brain activity that allows self-other distinction.

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease.

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.