Development of a PET Probe Targeting Bromodomain and Extra-Terminal Proteins for In Vitro and In Vivo Visualization.

Bromodomain and extra-terminal (BET) proteins are critical regulators of gene transcription, as they recognize acetylated lysine residues. The BD1 bromodomain of BRD4, a member of the BET family, has emerged as a promising therapeutic target for various diseases. This study aimed to develop and evaluate a novel C-11 labeled PET radiotracer, [C]YL10, for imaging the BD1 bromodomain of BRD4 in vivo.

Genetics of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage(ICH) represents a life-threatening form of stroke, marked by its impact on survival and quality of life. ICH can be categorized from monogenic disorders linked to causal germline variants in ICH-related genes to complex sporadic cases, highlighting the interaction among lifestyle factors, environmental influences, and genetic components in determining risk. Among sporadic ICH, the influence of these factors varies across ICH subtypes, evidenced by heritability rates of up to 73% for lobar ICH versus 34% for non-lobar ICH.

Inflammatory disease in people with multiple sclerosis treated with immune checkpoint inhibitors.

This study evaluated disease activity in people with Multiple Sclerosis (PwMS) who received immune checkpoint inhibitors (ICIs) compared to PwMS not treated with ICIs. There were 108 PwMS included (27 PwMS+ICIs and 81 PwMS controls), matched on age, sex, disease duration, DMTs, and MS disease course. Of 27 PwMS+ICIs, one (4%) had a relapse and four (15%) developed new MRI lesions without clinical symptoms.

Electrophysiological Insights into Alzheimer's Disease: A Review of Human and Animal Studies.

This review highlights the crucial role of neuroelectrophysiology in illuminating the mechanisms underlying Alzheimer's disease (AD) pathogenesis and progression, emphasizing its potential to inform the development of effective treatments. Electrophysiological techniques provide unparalleled precision in exploring the intricate networks affected by AD, offering insights into the synaptic dysfunction, network alterations, and oscillatory abnormalities that characterize the disease. We discuss a range of electrophysiological methods, from non-invasive clinical techniques like electroencephalography and magnetoencephalography to invasive recordings in animal models.

Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas.

Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer's disease and frontotemporal lobe degeneration from Latin America and the United States.

Association of social vulnerability and depression incidence post intracerebral haemorrhage: a cohort study.

Objectives: Survivors of intracerebral haemorrhage (ICH) are at high risk of incident depression, which is modified by social determinants of health (SDOH) and associated with worse functional outcomes. We sought to determine the role of prestroke SDOH in depression incidence after ICH to better characterise post-ICH outcomes.

Study Design: We analysed data from a cohort study of ICH survivors without prestroke depression, presenting at Massachusetts General Hospital between 2006 and 2017.

Genetic vulnerability and adverse mental health outcomes following mild traumatic brain injury: a meta-analysis of CENTER-TBI and TRACK-TBI cohorts.

Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes.

Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.

The onset presentation of multiple sclerosis differs in Hispanic/Latinx Americans compared with non-Hispanic White Americans.

Background: Little is known about how multiple sclerosis (MS) presents in Hispanic/Latinx (HL) people with MS (pwMS).

Objective: Compare age at onset (AAO) and onset severity between HL versus non-Hispanic White (NHW) pwMS.

Methods: A cross-sectional study leveraged the MS PATHS registry spanning seven US tertiary care institutions.

Stabilization of mitochondria-associated endoplasmic reticulum membranes regulates Aβ generation in a three-dimensional neural model of Alzheimer's disease.

Introduction: We previously demonstrated that regulating mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) affects axonal Aβ generation in a well-characterized three-dimensional (3D) neural Alzheimer's disease (AD) model. MAMs vary in thickness and length, impacting their functions. Here, we examined the effect of MAM thickness on Aβ in our 3D neural model of AD.

Search for a genetic cause of variably protease-sensitive prionopathy.

Variably protease-sensitive prionopathy (VPSPr) is a rare, atypical subtype of prion disease in which many patients exhibit a family history of dementia. Rare protein-coding variants in , which are causal for all known forms of genetic prion disease, have been ruled out in all VPSPr cases to date, leading to suspicion that VPSPr could be caused by variants in other genes or by non-coding variation in or near . We performed exome sequencing and targeted sequencing of non-coding regions on genomic DNA from autopsy-confirmed VPSPr patients (N=67) in order to search for a possible genetic cause.

Performance of study partner reports in a non-demented at-risk sample.

Introduction: The Clinical Dementia Rating (CDR) Scale is a gold standard for staging impairment in Alzheimer's disease and other dementias (ADRD). The Quick Dementia Rating System (QDRS) offers similar results in 3 to 5 minutes without a trained clinician. This study aimed to (1) investigate concordance between comparably derived QDRS and CDR global scores, (2) examine item-level QDRS/CDR agreement, and (3) compare sample characteristics and cognitive performance across QDRS/CDR global concordant/discordant groups.

Differential associations of neighborhood disadvantage, race/ethnicity, and cognitive status with experiences of psychosocial distress in the HABS-HD cohort.

Introduction: Understanding how contextual socioeconomic factors are associated with psychosocial distress among different ethnoracial groups is important for addressing health disparities in individuals at risk for Alzheimer's disease.

Methods: Using Health and Aging Brain Study-Health Disparities (HABS-HD) data collected between 2017 and 2023, we examined the association of neighborhood disadvantage with psychosocial distress using demographically adjusted linear regression models, stratified by ethnoracial group and cognitive status.

Results: We included 630 non-Hispanic Black, 1109 Hispanic, and 1068 non-Hispanic White older adults deemed cognitively normal (CN) or diagnosed with mild cognitive impairment (MCI).

A computational and multi-brain signature for aberrant social coordination in schizophrenia.

Social functioning impairment is a core symptom of schizophrenia (SCZ). Yet, the computational and neural mechanisms of social coordination in SCZ under real-time and naturalistic settings are poorly understood. Here, we instructed patients with SCZ to coordinate with a healthy control (HC) in a joint finger-tapping task, during which their brain activity was measured by functional near-infrared spectroscopy simultaneously.

Leveraging Stacked Classifiers for Multi-task Executive Function in Schizophrenia Yields Diagnostic and Prognostic Insights.

Cognitive impairment is a central characteristic of schizophrenia. Executive functioning (EF) impairments are often seen in mental disorders, particularly schizophrenia, where they relate to adverse outcomes. As a heterogeneous construct, how specifically each dimension of EF to characterize the diagnostic and prognostic aspects of schizophrenia remains opaque.

Body mass index trends over four years in persons with multiple sclerosis.

Background: The role of obesity in persons with multiple sclerosis (PwMS) is incompletely understood. Obesity predisposes individuals to a pro-inflammatory state and cardiovascular comorbidities, both of which can negatively impact MS disease course. A better understanding of weight trends in PwMS will inform optimal management of those who are overweight or obese.

Distinct roles of ascorbic acid in extracellular vesicles and free form: Implications for metabolism and oxidative stress in presymptomatic Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin gene. The huntingtin protein (Htt) is ubiquitously expressed and localized in several organelles, including endosomes, where it plays an essential role in intracellular trafficking. Presymptomatic HD is associated with a failure in energy metabolism and oxidative stress.

Redesigning Berberines and Sanguinarines to Target Soluble Epoxide Hydrolase for Enhanced Anti-Inflammatory Efficacy.

Amino-berberine has remained underexplored due to limited biological evaluation and total synthesis approaches. In inflammation therapy, soluble Epoxide Hydrolase (sEH) is a promising target, yet natural scaffolds remain underutilized. Our study advances the field by redesigning natural compounds─berberine and sanguinarine─with strategic urea modifications and hydrogenated frameworks, creating novel sEH inhibitors with enhanced efficacy.

Olfactory function is reduced in a subset of former elite American football players with traumatic encephalopathy syndrome.

Former American football players are at risk for developing traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The objective of this study was to determine whether hyposmia is present in traumatic encephalopathy syndrome. The study included 119 former professional American football players, 60 former college football players, and 58 same-age asymptomatic unexposed men from the DIAGNOSE CTE Research Project.

Sex differences in inter-temporal decision making and cortical thickness of the orbitofrontal and insula in young adult cannabis users: Evidence from 1111 subjects.

To test for sex differences in the impact of cannabis use on decision-making and brain correlates, we employed cortical thickness (CT) analysis of brain regions involved in intertemporal decision-making namely bilateral orbitofrontal cortex(OFC) and insula in young adult nondependent cannabis-users(CU) and non-users(NU) and their scores on delay discounting task. Neuroimaging analyzes of previously collected data were performed on 608CU and 503NU. CT analysis was performed on MRI images.

PrP turnover in vivo and the time to effect of prion disease therapeutics.

PrP lowering is effective against prion disease in animal models and is being tested clinically. Therapies in the current pipeline lower PrP production, leaving pre-existing PrP to be cleared according to its own half-life. We hypothesized that PrP's half-life may be a rate-limiting factor for the time to effect of PrP-lowering drugs, and one reason why late treatment of prion-infected mice is not as effective as early treatment.