The P200 ERP Response in Mild Cognitive Impairment and the Aging Population.

Evoked potential metrics extracted from an EEG exam can provide novel sources of information regarding brain function. While the P300 occurring around 300 ms post-stimulus has been extensively investigated in relation to mild cognitive impairment (MCI), with decreased amplitude and increased latency, the P200 response has not, particularly in an oddball-stimulus paradigm. This study compares the auditory P200 amplitudes between MCI (28 patients aged 74(8)) and non-MCI, (35 aged 72(4)).

β-Amyloid species production and tau phosphorylation in iPSC-neurons with reference to neuropathologically characterized matched donor brains.

A basic assumption underlying induced pluripotent stem cell (iPSC) models of neurodegeneration is that disease-relevant pathologies present in brain tissue are also represented in donor-matched cells differentiated from iPSCs. However, few studies have tested this hypothesis in matched iPSCs and neuropathologically characterized donated brain tissues. To address this, we assessed iPSC-neuron production of β-amyloid (Aβ) Aβ40, Aβ42, and Aβ43 in 24 iPSC lines matched to donor brains with primary neuropathologic diagnoses of sporadic AD (sAD), familial AD (fAD), control, and other neurodegenerative disorders.

Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia.

The stimulator of interferon genes (STING) pathway has been implicated in neurodegenerative diseases, including Parkinson's disease and amyotrophic lateral sclerosis (ALS). While prior studies have focused on STING within immune cells, little is known about STING within neurons. Here, we document neuronal activation of the STING pathway in human postmortem cortical and spinal motor neurons from individuals affected by familial or sporadic ALS.

Accelerated cascade melanoma therapy using enzyme-nanozyme-integrated dissolvable polymeric microneedles.

Dissolvable polymeric microneedles (DPMNs) have emerged as a powerful technology for the localized treatment of diseases, such as melanoma. Herein, we fabricated a DPMN patch containing a potent enzyme-nanozyme composite that transforms the upregulated glucose consumption of cancerous cells into lethal reactive oxygen species via a cascade reaction accelerated by endogenous chloride ions and external near-infrared (NIR) irradiation. This was accomplished by combining glucose oxidase (Gox) with a NIR-responsive chloroperoxidase-like copper sulfide (CuS) nanozyme.

Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's disease.

Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimer's disease. In Alzheimer's disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD.

Hypnosis and suggestion as interventions for functional neurological disorder: A systematic review.

Objective: Functional neurological disorder (FND) involves the presence of neurological symptoms that cannot be explained by neurological disease. FND has long been linked to hypnosis and suggestion, both of which have been used as treatments. Given ongoing interest, this review examined evidence for the efficacy of hypnosis and suggestion as treatment interventions for FND.

Dimensional clinical phenotyping using brain donor medical records: RDoC profiling is associated with Alzheimer's disease neuropathology.

Introduction: Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to work, as assessments of phenotypic concepts need to rely on existing records.

Methods: We adapted well-validated methodologies to compute National Institute of Mental Health Research Domain Criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from brain donors and tested whether cognitive domain scores were associated with Alzheimer's disease neuropathological measures.

Dimensional clinical phenotyping using post-mortem brain donor medical records: Association with neuropathology.

Introduction: Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to postmortem work, as assessment of newly developed phenotypic concepts needs to rely on existing records.

Methods: We adapted well-validated methodologies to compute NIMH research domain criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from post-mortem brain donors and tested whether RDoC cognitive domain scores were associated with hallmark Alzheimer's disease (AD) neuropathological measures.

Creating the Pick's disease International Consortium: Association study of H2 haplotype with risk of Pick's disease.

Background: Pick's disease (PiD) is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. PiD is pathologically defined by argyrophilic inclusion Pick bodies and ballooned neurons in the frontal and temporal brain lobes. PiD is characterised by the presence of Pick bodies which are formed from aggregated, hyperphosphorylated, 3-repeat tau proteins, encoded by the gene.

Plasma biomarkers for diagnosis of Alzheimer's disease and prediction of cognitive decline in individuals with mild cognitive impairment.

Background: The last few years have seen major advances in blood biomarkers for Alzheimer's Disease (AD) with the development of ultrasensitive immunoassays, promising to transform how we diagnose, prognose, and track progression of neurodegenerative dementias.

Methods: We evaluated a panel of four novel ultrasensitive electrochemiluminescence (ECL) immunoassays against presumed CNS derived proteins of interest in AD in plasma [phosphorylated-Tau181 (pTau181), total Tau (tTau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)]. Two sets of banked plasma samples from the Massachusetts Alzheimer's Disease Research Center's longitudinal cohort study were examined: A longitudinal prognostic sample ( = 85) consisting of individuals with mild cognitive impairment (MCI) and 4 years of follow-up and a cross-sectional sample ( = 238) consisting of individuals with AD, other neurodegenerative diseases (OND), and normal cognition (CN).

Common mouse models of tauopathy reflect early but not late human disease.

Background: Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer's Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level.

Methods: We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics.

Electrophysiological trajectories of concussion recovery: From acute to prolonged stages in late teenagers.

Purpose: Numerous studies have reported electrophysiological differences between concussed and non-concussed groups, but few studies have systematically explored recovery trajectories from acute concussion to symptom recovery and the transition from acute concussion to prolonged phases. Questions remain about recovery prognosis and the extent to which symptom resolution coincides with injury resolution. This study therefore investigated the electrophysiological differences in recoveries between simple and complex concussion.

Using fixed-potential electrodes to quantify iron and manganese redox cycling in upland soils.

Although metal redox reactions in soils can strongly affect carbon mineralization and other important soil processes, little is known about temporal variations in this redox cycling. Recently, potentiostatically poised electrodes (fixed-potential electrodes) have shown promise for measuring the rate of oxidation and reduction at a specific reduction potential in situ in riparian soils. Here for the first time, we used these electrodes in unsaturated soils to explore the fine-scale temporal redox fluctuations of both iron and manganese in response to environmental conditions.

A correlation map of genome-wide DNA methylation patterns between paired human brain and buccal samples.

Epigenome-wide association studies (EWAS) assessing the link between DNA methylation (DNAm) and phenotypes related to structural brain measures, cognitive function, and neurodegenerative diseases are becoming increasingly more popular. Due to the inaccessibility of brain tissue in humans, several studies use peripheral tissues such as blood, buccal swabs, and saliva as surrogates. To aid the functional interpretation of EWAS findings in such settings, there is a need to assess the correlation of DNAm variability across tissues in the same individuals.

Assessment of cholesterol homeostasis in the living human brain.

Alterations in brain cholesterol homeostasis have been broadly implicated in neurological disorders. Notwithstanding the complexity by which cholesterol biology is governed in the mammalian brain, excess neuronal cholesterol is primarily eliminated by metabolic clearance via cytochrome P450 46A1 (CYP46A1). No methods are currently available for visualizing cholesterol metabolism in the living human brain; therefore, a noninvasive technology that quantitatively measures the extent of brain cholesterol metabolism via CYP46A1 could broadly affect disease diagnosis and treatment options using targeted therapies.

Editing reality in the brain.

Recent information technologies such as virtual reality (VR) and augmented reality (AR) allow the creation of simulated sensory worlds with which we can interact. Using programming language, digital details can be overlaid onto displays of our environment, confounding what is real and what has been artificially engineered. Natural language, particularly the use of direct verbal suggestion (DVS) in everyday and hypnotic contexts, can also manipulate the meaning and significance of objects and events in ourselves and others.

Mapping the Spatial Distribution of Fibrillar Polymorphs in Human Brain Tissue.

Alzheimer's disease (AD) is a neurodegenerative disorder defined by the progressive formation and spread of fibrillar aggregates of Aβ peptide and tau protein. Polymorphic forms of these aggregates may contribute to disease in varying ways since different neuropathologies appear to be associated with different sets of fibrillar structures and follow distinct pathological trajectories that elicit characteristic clinical phenotypes. The molecular mechanisms underlying the spread of these aggregates in disease may include nucleation, replication, and migration all of which could vary with polymorphic form, stage of disease, and region of brain.

"You Forget to Apply It to Staff": A Compassion-Focused Group for Mental Health Inpatient Staff. An Exploration of the Barriers to Attendance.

This study explored the feasibility and acceptability of an experiential compassion-focused group intervention for mental health inpatient staff. Findings demonstrated that although participants found sessions enjoyable, and reported a number of benefits, the group attrition was high. Semi-structured interviews were conducted to explore issues related to group dropout.

Somatic genomic changes in single Alzheimer's disease neurons.

Dementia in Alzheimer's disease progresses alongside neurodegeneration, but the specific events that cause neuronal dysfunction and death remain poorly understood. During normal ageing, neurons progressively accumulate somatic mutations at rates similar to those of dividing cells which suggests that genetic factors, environmental exposures or disease states might influence this accumulation. Here we analysed single-cell whole-genome sequencing data from 319 neurons from the prefrontal cortex and hippocampus of individuals with Alzheimer's disease and neurotypical control individuals.