Infants on the move: bibliometric analyses of observational vs. digital means of screening infant development.

Neurodevelopmental disorders are on the rise, yet their average diagnosis is after 4.5 years old. This delay is partly due to reliance on social-communication criteria, which require longer maturation than scaffolding elements of neuromotor control.

Pros and cons of narrow- versus wide-compartment rotarod apparatus: An experimental study in mice.

The rotarod test, a sensorimotor assessment that allows for quantitative evaluation of motor coordination in rodents, has extensive application in many research fields. The test results exhibit extreme between-study variability, sometimes making it challenging to conclude the validity of certain disease models and related therapeutic effects. Although the variation in test paradigms may account for this disparity, some features of rotarod apparatus including rod diameter make differences.

Tau and Alzheimer's disease: Past, present and future.

My journey with tau started when in 1974 for the first time I isolated neurofibrillary tangles of paired helical filaments (PHFs) from autopsied Alzheimer's disease (AD) brains and discovered that they were made up of a ~50-70 KDa protein on SDS-polyacrylamide gels. Subsequently my team discovered that this PHF protein and the microtubule-associated factor called tau were one and the same protein. However, we found that tau in neurofibrillary tangles/PHFs in AD brain was abnormally hyperphosphorylated, and unlike normal tau, which promoted the assembly of tubulin into microtubules, the AD-hyperphosphorylated tau inhibited microtubule assembly.

c-Src regulates δ-secretase activation and truncated Tau production by phosphorylating the E3 ligase Traf6.

The accumulation of abnormal Tau protein is a common feature of various neurodegenerative diseases. Truncated Tau, resulting from cleavage by asparaginyl endopeptidase (AEP, δ-secretase), promotes its own phosphorylation and aggregation. Our study focused on understanding the regulatory mechanisms of AEP activation and its interaction with other proteins.

Tau truncation in the pathogenesis of Alzheimer's disease: a narrative review.

Alzheimer's disease is characterized by two major neuropathological hallmarks-the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer's disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics.

Obesity, diabetes and their metabolic correlates in middle-aged adults with Down syndrome.

Background: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile.

Methods: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.

4-AP challenge reveals that early intervention with brivaracetam prevents posttraumatic epileptogenesis in rats.

Purpose: There are currently no clinical treatments to prevent posttraumatic epilepsy (PTE). Recently, our group has shown that administration of levetiracetam (LEV) or brivaracetam (BRV) shortly after cortical neurotrauma prevents the development of epileptiform activity in rats, as measured ex vivo in neocortical slices. Due to the low incidence of spontaneous seizures in rodent-based models of traumatic brain injury (TBI), chemoconvulsants have been used to test injured animals for seizure susceptibility.

Early social referencing predicts object mastery motivation in infancy: Social antecedents of object mastery motivation.

The researchers sought to understand the typical development of social referencing and object mastery motivation in infancy and to determine the relationship between social referencing and object mastery behaviors in infants from 7 to 22 months of age. The study included 36 infants who were followed as part of a longitudinal study of at-risk infants but were not determined to need care in the neonatal intesive care unit at birth. Both mastery behaviors of persistence and success showed a statistically significant effect of age, while social behaviors remained stable from 7 to 22 months.

Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by Tyr-phosphorylated APP βCTF.

Lysosome dysfunction arises early and propels Alzheimer's disease (AD). Herein, we show that amyloid precursor protein (APP), linked to early-onset AD in Down syndrome (DS), acts directly via its β-C-terminal fragment (βCTF) to disrupt lysosomal vacuolar (H)-adenosine triphosphatase (v-ATPase) and acidification. In human DS fibroblasts, the phosphorylated YENPTY internalization motif of APP-βCTF binds selectively within a pocket of the v-ATPase V0a1 subunit cytoplasmic domain and competitively inhibits association of the V1 subcomplex of v-ATPase, thereby reducing its activity.

Individualized estimated years from onset of Alzheimer's disease- related decline for adults with Down syndrome.

Introduction: Adults with Down syndrome (DS) are at increased risk for Alzheimer's disease (AD) and vary in their age of transition from AD preclinical to prodromal or more advanced clinical stages. An empirically based method is needed to determine individual "estimated years from symptom onset (EYO)," the same construct used in studies of autosomal dominant AD .

Methods: Archived data from a previous study of > 600 adults with DS were examined using survival analysis methods.

High performing male with fragile X syndrome with an unmethylated full mutation: The relevance of clinical and genetic correlations.

A high performing male with an unmethylated full mutation in the fragile X messenger ribonucleoprotein 1 () gene surpassed our expectations into young adulthood. Although initial genetic findings helped make a correct fragile X syndrome (FXS) determination, the report was insufficient. Ten years later, we repeated and conducted additional genetic and clinical studies to determine whether more information could assist with treatment and counseling.

C9orf72 poly-PR helps p53 escape from the ubiquitin-proteasome system and promotes its stability.

C9orf72-derived dipeptide repeats (DPRs) proteins have been regarded as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). As the most toxic DPRs in C9-ALS/FTD, poly-proline-arginine (poly-PR) is associated with the stability and accumulation of p53, which consequently induces neurodegeneration. However, the exact molecular mechanism via which C9orf72 poly-PR stabilizes p53 remains unclear.

Intraneuronal accumulation of amyloid-β peptides as the pathomechanism linking autism and its co-morbidities: epilepsy and self-injurious behavior - the hypothesis.

Autism spectrum disorder (ASD) is associated with enhanced processing of amyloid-β precursor protein (APP) by secretase-α, higher blood levels of sAPPα and intraneuronal accumulation of N-terminally truncated Aβ peptides in the brain cortex - mainly in the GABAergic neurons expressing parvalbumin - and subcortical structures. Brain Aβ accumulation has been also described in epilepsy-the frequent ASD co-morbidity. Furthermore, Aβ peptides have been shown to induce electroconvulsive episodes.

Does modulation of tau hyperphosphorylation represent a reasonable therapeutic strategy for Alzheimer's disease? From preclinical studies to the clinical trials.

Protein kinases (PKs) have emerged as one of the most intensively investigated drug targets in current pharmacological research, with indications ranging from oncology to neurodegeneration. Tau protein hyperphosphorylation was the first pathological post-translational modification of tau protein described in Alzheimer's disease (AD), highlighting the role of PKs in neurodegeneration. The therapeutic potential of protein kinase inhibitors (PKIs)) and protein phosphatase 2 A (PP2A) activators in AD has recently been explored in several preclinical and clinical studies with variable outcomes.

CAG Repeat Expansion in THAP11 Is Associated with a Novel Spinocerebellar Ataxia.

Background: More than 50 loci are associated with spinocerebellar ataxia (SCA), and the most frequent subtypes share nucleotide repeats expansion, especially CAG expansion.

Objective: The objective of this study was to confirm a novel SCA subtype caused by CAG expansion.

Methods: We performed long-read whole-genome sequencing combined with linkage analysis in a five-generation Chinese family, and the finding was validated in another pedigree.

Two simple assays for assessing the seeding activity of proteopathic tau.

The regional distribution of neurofibrillary tangles of hyperphosphorylated tau aggregates is associated with the progression of Alzheimer's disease (AD). Misfolded proteopathic tau recruits naïve tau and templates its misfolding and aggregation in a prion-like fashion, which is believed to be the molecular basis of propagation of tau pathology. A practical way to assess tau seeding activity is to measure its ability to recruit/bind other tau molecules and to induce tau aggregation.

Downregulation of cyclic adenosine monophosphate levels in leukocytes of hibernating captive black bears is similar to reported cyclic adenosine monophosphate findings in major depressive disorder.

Introduction: Cyclic adenosine monophosphate (cAMP) levels in the lymphoblasts and leukocytes of patients with major depressive disorder (MDD) have been reported to be downregulated compared to in controls. cAMP is a derivative of adenosine triphosphate (ATP), and low ATP turnover has been reported in the state of hypometabolism associated with human MDD and with mammalian hibernation due to suppression of mitochondrial metabolism. Similarities have been noted between many state-dependent neurobiological changes associated with MDD in humans and with mammalian hibernation.

Development of Novel Fluorinated Polyphenols as Selective Inhibitors of DYRK1A/B Kinase for Treatment of Neuroinflammatory Diseases including Parkinson's Disease.

Natural polyphenol derivatives such as those found in green tea have been known for a long time for their useful therapeutic activity. Starting from EGCG, we have discovered a new fluorinated polyphenol derivative () characterized by improved inhibitory activity against DYRK1A/B enzymes and by considerably improved bioavailability and selectivity. DYRK1A is an enzyme that has been implicated as an important drug target in various therapeutic areas, including neurological disorders (Down syndrome and Alzheimer's disease), oncology, and type 2 diabetes (pancreatic β-cell expansion).

Phenotypic variability and gastrointestinal manifestations/interventions for growth in NAA10-related neurodevelopmental syndrome.

Our study of 61 children with NAA10-related neurodevelopmental syndrome, an X-linked disorder due to NAA10 gene variants, demonstrated a high prevalence of growth failure, with weight and height percentiles often in the failure-to-thrive diagnostic range; however, dramatic weight fluctuations and phenotypic variability is evidenced in the growth parameters of this population. Although never previously explored in depth, the gastrointestinal pathology associated with NAA10-related neurodevelopmental syndrome includes feeding difficulties in infancy, dysphagia, GERD/silent reflux, vomiting, constipation, diarrhea, bowel incontinence, and presence of eosinophils on esophageal endoscopy, in order from most to least prevalent. Additionally, the gastrointestinal symptom profile for children with this syndrome has been expanded to include eosinophilic esophagitis, cyclic vomiting syndrome, Mallory Weiss tears, abdominal migraine, esophageal dilation, and subglottic stenosis.

Passive immunization inhibits tau phosphorylation and improves recognition learning and memory in 3xTg-AD mice.

Tau pathology is essential in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Tau immunotherapy aimed at reducing the progression of tau pathology provides a potential therapeutic strategy for treating these diseases. By screening monoclonal antibodies 43D, 63B, 39E10, and 77G7 that recognize epitopes ranging from tau's N-terminus to C-terminus, we found the 77G7, which targets the microtubule-binding domain promoted tau clearance in a dose-dependent manner by entering neuronal cells in vitro.