Recent ucsdsom_nrs_oapdeposits items

Author Correction: Large-scale network analysis of the cerebrospinal fluid proteome identifies molecular signatures of frontotemporal lobar degeneration

Mon, 27 Jul 2026 00:00:00 +0000

Correction to: Nature Aginghttps://doi.org/10.1038/s43587-025-00878-2, published online 16 May 2025. This article was originally published under standard Springer Nature license (© The Author(s), under exclusive licence to Springer Nature America, Inc.). It is now available as an open-access paper under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license, © The Author(s). The error has been corrected in the HTML and PDF versions of the article.

Eating Disorders and Parkinson's Disease-1: Comorbidities, Neurobiology, and Family History.

Fri, 5 Jun 2026 00:00:00 +0000

Objective

Eating disorders (ED), particularly anorexia nervosa (AN), share neurobiological characteristics with Parkinson's Disease (PD) (e.g., premorbid anxiety, dopaminergic dysfunction, harm avoidance, weight loss), suggesting common vulnerability. The present study built upon these observations, an AN patient's reported family history of Parkinson's Disease (RFHoPD), and AN:PD genetic correlation estimates, by ascertaining RFHoPD in families of individuals with PD.

Method

We ascertained RFHoPD among ED patients and community participants, and estimated relative risks (RRs) for AN, Bulimia Nervosa (BN), and Binge Eating Disorder (BED).

Results

In the total sample (N = 1135), we observed increased RFHoPD among patients and community participants meeting criteria for ED diagnoses (n = 727) versus community participants without an ED diagnosis (n = 408). For AN, RFHoPD prevalence was 6.6%, versus 3.4% (χ² = 4.638,...

Clinical and pathologic correlations of machine learning quantification of Aβ deposits across 3 brain regions of decedents with Alzheimer disease

Mon, 27 Apr 2026 00:00:00 +0000

Machine learning enables scalable quantification of neuropathology, offering deeper phenotyping of Alzheimer's disease (AD). In this validation study, we quantified amyloid-beta (Aβ) deposits, evaluating multiple brain regions across institutions, and evaluated associations with clinical, demographic, and genetic factors in persons pathologically diagnosed with AD. All linear models were adjusted for sex, age of death, ethnicity, and center. We analyzed densities (#/mm2) of cored plaques, diffuse plaques, and cerebral amyloid angiopathy (CAA) in 273 individuals from 3 Alzheimer's Disease Research Centers. Formalin-fixed paraffin-embedded sections of frontal, temporal, and parietal cortices were immunostained and digitized, generating 799 whole-slide images (WSIs). Following log transformation, mixed-effects modeling revealed the parietal cortex had the highest cored plaque densities (P < .001); the temporal cortex had the highest diffuse plaque (P < .001); CAA showed no...

An Algorithm for Automated Measurement of Kinetic Tremor Magnitude Using Digital Spiral Drawings

Thu, 23 Apr 2026 00:00:00 +0000

Introduction: Essential tremor is a common movement disorder. Numerous validated clinical rating scales exist to quantify essential tremor severity by employing rater-dependent visual observation but have limitations, including the need for trained human raters and the lack of precision and sensitivity compared to technology-based objective measures. Other continuous objective methods to quantify tremor amplitude have been developed, but frequently provide unitless measures (e.g., tremor power), limiting real-world interpretability. We propose a novel algorithm to measure kinetic tremor amplitude using digital spiral drawings, applying the V3 framework (sensor verification, analytical validation, and clinical validation) to establish reliability and clinical utility. Methods: Archimedes spiral drawings were recorded on a digitizing tablet from participants (n = 7) enrolled in a randomized placebo control double-blinded crossover pilot trial evaluating the efficacy of oral...

The 2024 Brain Tumor Segmentation (BraTS) Challenge: Glioma Segmentation on Post-treatment MRI

Thu, 23 Apr 2026 00:00:00 +0000

Gliomas are the most common malignant primary brain tumors in adults and one of the deadliest types of cancer. There are many challenges in treatment and monitoring due to the genetic diversity and high intrinsic heterogeneity in appearance, shape, histology, and treatment response. Treatments include surgery, radiation, and systemic therapies, with magnetic resonance imaging (MRI) playing a key role in treatment planning and post-treatment longitudinal assessment. The 2024 Brain Tumor Segmentation (BraTS) challenge on post-treatment glioma MRI will provide a community standard and benchmark for state-of-the-art automated segmentation models based on the largest expert-annotated post-treatment glioma MRI dataset. Challenge competitors will develop automated segmentation models to predict four distinct tumor sub-regions consisting of enhancing tissue (ET), surrounding non-enhancing T2/fluid-attenuated inversion recovery (FLAIR) hyperintensity (SNFH), non-enhancing tumor core (NETC),...

Association of neurogenic orthostatic hypotension with cognitive decline in Parkinson’s disease: a longitudinal cohort study

Thu, 23 Apr 2026 00:00:00 +0000

Neurogenic orthostatic hypotension (nOH), a common non-motor feature of Parkinson’s disease (PD), is defined as a sustained drop in blood pressure (BP) upon standing due to autonomic dysfunction. Although prior studies support an association between nOH and cognitive impairment, its longitudinal impact on cognitive decline in PD remains insufficiently explored. We aimed to determine to what extent baseline nOH is associated with an accelerated decline in global and exploratory domain-specific cognitive functions. A retrospective longitudinal cohort study was conducted using clinical data from patients with PD evaluated at the University of California San Diego movement disorders clinics between 2012 and 2024. Participants were classified as having nOH (nOH+) or without nOH (nOH−) based on initial orthostatic BP measurements (≥20 mmHg systolic BP and/or ≥10 mmHg diastolic BP reduction within 3 minutes of standing, with a blunted heart rate response [ΔHR/ΔSBP] < 0.5 bpm/mmHg)....

Acute Pharmacodynamic Effects of Oral Levodopa on Blood Pressure in Parkinson's Disease

Thu, 23 Apr 2026 00:00:00 +0000

BACKGROUND: Levodopa decreases blood pressure (BP) in persons with Parkinson's disease (PwP), but no pharmacodynamic studies integrating systemic levodopa concentration measurements have characterized its hypotensive effects. Understanding this relationship is clinically relevant for guiding therapeutic decisions, such as how aggressively to treat hypotension before initiating or increasing levodopa. In this pilot study, we aimed to determine the acute pharmacodynamic effects of oral immediate-release carbidopa/levodopa on BP in PwP. METHODS: PwP taking chronic oral carbidopa/levodopa with baseline BP ≥ 90/60 mmHg were recruited. Participants withheld antiparkinsonian medications overnight prior to the study visit and received carbidopa/levodopa immediate-release tablets at time 0. Capillary blood levodopa levels, seated BP measurements, and motor symptom assessments were performed at baseline and repeated every 10 min for 70-100 min. Non-compartmental pharmacokinetic parameters...

The Oldest Known Case of SCA6: Diagnostic Insights from a 101‐Year‐Old Woman with Progressive Ataxia

Thu, 23 Apr 2026 00:00:00 +0000

The Oldest Known Case of SCA6: Diagnostic Insights from a 101‐Year‐Old Woman with Progressive Ataxia

Impact of clinical neurophysiological assessment on diagnosis and management of tremor disorders

Thu, 23 Apr 2026 00:00:00 +0000

Objective: To assess the clinical utility of a standardized, non-invasive electrodiagnostic testing protocol in refining the diagnosis and management of patients referred for tremor evaluation. Methods: In this prospective observational study, patients with tremulous limb movements with indeterminate clinical diagnoses involving tremor as a cardinal symptom were referred by movement disorders neurologists. Participants underwent standardized phenotyping and electrodiagnostic studies for tremor analysis including four-channel surface electromyography polygraphy and two-channel accelerometry. Results: Clinical and electrophysiological data from 31 consecutive individuals were analyzed. Electrodiagnostic testing refined the differential diagnosis in 25/31 (80.6 %) participants and changed therapy in 14/29 (48.3 %). Changes included adjusting pharmacotherapy (n = 10), undergoing deep brain stimulation surgery (n = 2), or avoiding invasive procedures (n = 2). Conclusions:...

Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.

Wed, 1 Apr 2026 00:00:00 +0000

Axons are unique structural and functional features of nerve cells, which play a critical role in regulating neuronal homeostasis. Dysfunction and degeneration of axons (axonopathy) has been established as an early and prominent contributing mechanism to the pathogenesis of neurodegenerative diseases including Alzheimers disease, Parkinsons disease, Huntingtons disease, and amyotrophic lateral sclerosis. In this review, we briefly summarize the structure and function of axons, and highlight recent advances in the understanding of the role of axons in health and disease. We argue that axons are a potential target for developing novel therapies for neurodegenerative diseases.

Endogenous Lithium Levels and Alzheimer Disease

Thu, 26 Mar 2026 00:00:00 +0000

Endogenous Lithium Levels and Alzheimer Disease

The Diagnosis and Management of Reversible Dementia Syndromes

Thu, 26 Mar 2026 00:00:00 +0000

Purpose of ReviewThis article discusses the diagnostic evaluation and management of reversible dementia syndromes. It highlights clinical syndromes and explores the recent literature implicating certain reversible factors in Alzheimer’s disease pathogenesis.Recent FindingsThe prevalence of fully reversible dementia is low, but there is growing awareness for potentially reversible contributors to neurodegenerative disease. In particular, exposure to anticholinergic medications, obstructive sleep apnea, and depression have emerged as potentially modifiable targets in the pathogenesis of preclinical and early Alzheimer’s disease. Treatment of these factors may not only reverse any direct cognitive effects but also prevent downstream neurodegeneration.SummaryThere is substantial opportunity to improve outcome in patients with dementia due to reversible etiologies. Even in the setting of primary neurodegenerative disease, conscientious effort is required to recognize and address reversible...

Individualized Atrophy‐Based Prediction of Dementia Progression in Familial Frontotemporal Lobar Degeneration With Bayesian Linear Mixed‐Effects Modeling

Tue, 24 Mar 2026 00:00:00 +0000

OBJECTIVE: Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f-FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f-FTLD. We used a Bayesian linear mixed-effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. METHODS: Participants included 234 asymptomatic or prodromal carriers of C9orf72, GRN, or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1-weighted scans. The BLME models established individual voxel-wise gray matter trajectories using the first 2 scans. Person-specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time-varying Cox proportional hazard models covarying for age....

Potential role of MRI to optimize clinical trial design for progressive supranuclear palsy and corticobasal degeneration

Thu, 26 Feb 2026 00:00:00 +0000

BACKGROUND: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are 4-repeat tauopathies (4RT) presenting with overlapping syndromes. Imperfect clinicopathological associations increase sample-size demands in clinical trials. We test whether MRI can enrich trials for PSP/CBD and provide sensitive MRI-based outcome measures. METHODS: Longitudinal cohort analysis including participants from the 4 Repeat Tauopathy Neuroimaging Initiative (4RTNI) and phase 2/3 Davunetide trial (DAV). An MRI model trained on autopsy-confirmed cases predicted PSP (MRI-PSP) or CBD (MRI-CBD); corticobasal syndrome (CBS) with positive Alzheimer's biomarkers was reclassified. Clinical scales and MRI-derived thickness/volume were analyzed with linear mixed-effects models. We derived data-driven MRI-signatures (optimal regional combinations) to minimize required trial sample sizes. RESULTS: 206 participants from 4RTNI (n = 106 with Richardson's syndrome [RS], CBS, or nonfluent/agrammatic...

Progression of two Progressive Supranuclear Palsy phenotypes with comparable initial disability

Tue, 24 Feb 2026 00:00:00 +0000

INTRODUCTION: To avoid bias and optimize statistical power of disease-modifying therapeutic trials, it is critical to include homogeneous populations with similar rate of progression over time. Patients with Progressive Supranuclear Palsy (PSP)-Parkinsonism phenotype have overall slower disease progression than those with PSP-Richardson syndrome phenotype. However, it is unclear if the progression rate of PSP-Parkinsonism is the same when the PSP-Parkinsonism converts to PSP Richardson syndrome. We aimed to determine and compare disease progression rate of patients with the two most common PSP phenotypes: PSP-Parkinsonism and PSP Richardson syndrome, participating in the TAUROS trial. METHODS: 138 patients, 56 with PSP-Parkinsonism and 82 with PSP-Richardson syndrome, with similar clinical severity at baseline, were followed up to 60 weeks. PSP-Parkinsonism allocation was based on experts' judgement and PSP-Richardson on probable NINDS-PSP criteria. Global disease progression...

Harnessing the Neurobiology of Empathy and Compassion to Alleviate Burnout in Neurology

Sun, 15 Feb 2026 00:00:00 +0000

Neurologists regularly care for patients with complex, chronic, and often incurable conditions. These circumstances impose profound emotional burdens on the patient and physician. Whereas empathy is central to therapeutic effectiveness in clinical practice, sustained empathic engagement can contribute to emotional exhaustion and physician burnout, a condition now endemic in neurology. This review synthesizes insights from neuroscience, psychology, and clinical education to propose "skillful empathy" as a trainable capacity that integrates affective resonance with cognitive perspective-taking. We describe how emotional contagion harms clinician well-being and advocate for the integration of empathy training into medical education to support sustainable, compassionate neurological care. ANN NEUROL 2025.

Cannabidiol blood metabolite levels after cannabidiol treatment are associated with broadband EEG changes and improvements in visuomotor and non-verbal cognitive abilities in boys with autism requiring higher levels of support

Thu, 12 Feb 2026 00:00:00 +0000

Oral cannabidiol (CBD) treatment has been suggested to alleviate severe symptoms of autism spectrum disorder (ASD). While many CBD preparations have been studied in clinical trials involving ASD, none has used purified CBD preparations or preparations approved by the U.S. Food and Drug Administration, nor have they focused on children with ASD with higher support needs. Previous studies have identified several candidate electrophysiological biomarkers of cognitive and behavioral disabilities in ASD, with emerging biomarkers including periodic (oscillatory) and aperiodic measures of neural activity. We analyzed electroencephalography (EEG) recordings from 24 boys with ASD and higher support needs (aged 7–14 years) from a prior double-blind, placebo-controlled, crossover Phase II Clinical Trial (NCT04517799) that investigated whether 8 weeks of daily CBD treatment (up to 20 mg/kg/day) improved severe behavioral problems, measured at baseline, post-CBD, post-placebo, and post-washout....

Early subtypes and progressions of progressive supranuclear palsy: a data-driven brain bank study

Thu, 22 Jan 2026 00:00:00 +0000

BackgroundProgressive supranuclear palsy (PSP) is typically characterized by vertical supranuclear gaze palsy and early falls, referred to as Richardson’s syndrome (PSP-RS). Other presentations include postural instability (PSP-PI), Parkinsonism (PSP-P), speech/language disorder (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). However, differences across the early presentations and their subsequent clinical courses remain to be elucidated.ObjectiveThis study aimed to characterize early PSP subtypes and their subsequent progressions using a large postmortem dataset.MethodsAn automated pipeline incorporating fine-tuned Chat Generative Pretrained Transformer (ChatGPT) was developed. The pipeline collected 195 clinical features with onset information from autopsy-confirmed PSP cases without significant neurodegenerative co-pathologies.ResultsA structured clinicopathologic dataset from 588 patients was analyzed. The results...

Cognitive Function as a Predictor of Incident Hypertension in Hispanic/Latino Adults: Results From the Community Health Study/Study of Latinos.

Thu, 15 Jan 2026 00:00:00 +0000

BACKGROUND: Studies showed that hypertension predicts cognitive performance. It remains uncertain whether a bidirectional relationship exists. We investigated whether cognitive function predicts incident hypertension. METHODS: Data from the Hispanic Community Health Study/Study of Latinos were analyzed. Global cognitive score (GC) of nonhypertensive participants at baseline was derived by averaging z scores across 4 neurocognitive tests (brief Spanish-English verbal learning test sum and recall, word fluency, and digit symbol substitution test). Incident hypertension was investigated, on average, 6 years later. Sociodemographic characteristics and unhealthy behaviors (obesity, physical activity not at goal, low diet quality, smoking) were ascertained at baseline. Association of GC at baseline with incident hypertension (defined as blood pressure ≥130/80 mm Hg or on treatment) was investigated using logistic regression analyses adjusted for sociodemographic characteristics and...

Celebrating neuropathology's contributions to Alzheimer's Disease Research Centers

Thu, 15 Jan 2026 00:00:00 +0000

Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical-pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease-modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches....

Alzheimer Disease Biomarkers and Subjective Cognitive Decline Among Hispanic and/or Latino Adults

Thu, 15 Jan 2026 00:00:00 +0000

Importance: Subjective cognitive decline (SCD) may be an early indicator of Alzheimer disease and related dementias (ADRD), yet its association with plasma biomarkers remains unclear among middle-aged and older adults (aged 50-86 years). Objective: To examine associations between plasma biomarkers of amyloid, tau, neuroaxonal damage, and glial activation with SCD in a heterogeneous cohort of Hispanic and/or Latino adults. Design, Setting, and Participants: This cross-sectional study used survey-weighted data from the Study of Latinos-Investigation of Neurocognitive Aging, an ancillary study of the Hispanic Community Health Study/Study of Latinos. Participants were aged 50 to 86 years and resided in 4 major US cities. Data were collected from 2016 to 2018 and analyzed between December 2024 and June 2025. Exposure: Plasma biomarkers included amyloid-beta (Aβ42/40), phosphorylated tau-181 (ptau-181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP), quantified...

RAB5 Hyperactivation Induces APP‐Driven Endolysosomal and Autophagic Dysfunction in Down Syndrome: Reversal by Antisense Oligonucleotides Targeting App and Rab5

Thu, 15 Jan 2026 00:00:00 +0000

BACKGROUND: Down syndrome (DS) significantly increases the risk of Alzheimer's disease (DS-AD), with dysfunctions in the endolysosomal network (ELN) and autophagy pathways playing central roles in its pathogenesis. Dysregulation of the ELN, particularly involving RAB5 and lysosomal cathepsins, has been implicated in DS-AD, but the specific role of RAB5 hyperactivation remains poorly understood. METHODS: Postmortem brain samples from individuals with DS, DS-AD, a partial trisomy 21 case, and the Dp16 DS mouse model were examined to assess the impact of APP gene dosage on ELN and autophagy. We measured RAB5 activation, the activity of RAB7 and RAB11, their guanine nucleotide exchange factors (GEFs), lysosomal cathepsins, and autophagy-related pathways. Additionally, Dp16 mice were treated with App- and Rab5-specific antisense oligonucleotides (ASOs) to evaluate their therapeutic potential. RESULTS: Our findings revealed substantial ELN dysfunction in both DS and Dp16 brains, characterized...

A user's guide for α‐synuclein biomarker studies in biological fluids: Perianalytical considerations

Thu, 15 Jan 2026 00:00:00 +0000

Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summarizes perianalytical considerations for biomarker studies (based on immunoassays) in Parkinson's disease, with emphasis on quantifying total α-synuclein protein in biological fluids. Current knowledge and pitfalls are discussed, and selected perianalytical variables are presented systematically, including different temperature of sample collection and types of collection tubes, gradient sampling, the addition of detergent, aliquot volume, the freezing time, and the different thawing methods. We also discuss analytical confounders. We identify gaps in the knowledge and delineate specific areas that require further investigation, such as the need to identify posttranslational modifications of α-synuclein and antibody-independent...

Spatially heterogeneous acetylcholine dynamics in the striatum promote behavioral flexibility

Fri, 26 Dec 2025 00:00:00 +0000

Being able to switch from established choices to new alternatives when conditions change – behavioral flexibility – is essential for survival. Cholinergic signaling in the striatum contributes to such flexible behavior, yet the timing and spatial organization of acetylcholine release during contingency changes remain unclear, limiting conceptual understanding of its role in behavioral flexibility. Using a genetically encoded acetylcholine sensor and 2-photon imaging in the dorsal striatum of behaving mice, we visualized acetylcholine dynamics during acquisition and reversal learning in a virtual reality Y-maze. Rewarded outcomes evoked phasic decreases in acetylcholine, whereas unexpected non-reward following reversal triggered widespread increases that predicted lose-shift behavior. Targeted inhibition of cholinergic interneurons reduced this adaptive response. Spatial analysis revealed heterogeneous, temporally distinct signals forming functionally diverse microdomains. These...

TDP-43 loss induces cryptic polyadenylation in ALS/FTD

Sat, 20 Dec 2025 00:00:00 +0000

Nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 are cellular hallmarks of amyotrophic lateral sclerosis (ALS). TDP-43 nuclear loss causes de-repression of cryptic exons, yet cryptic alternative polyadenylation (APA) events have been largely overlooked. In this study, we developed a bioinformatic pipeline to reliably identify alternative last exons, 3’ untranslated region (3’UTR) extensions and intronic polyadenylation APA event types, and we identified cryptic APA sites induced by TDP-43 loss in induced pluripotent stem cell (iPSC)-derived neurons. TDP-43 binding sites are enriched at sites of these cryptic events, and TDP-43 can both repress and enhance APA. All categories of cryptic APA were also identified in ALS and frontotemporal dementia (FTD) postmortem brain tissue. RNA sequencing (RNA-seq), thiol(SH)-linked alkylation for the metabolic sequencing of RNA (SLAM-seq) and ribosome profiling (Ribo-seq) revealed that distinct cryptic APA categories...

Three-dimensional forward-scattering imaging flow cytometry system for single-cell analysis

Fri, 19 Dec 2025 00:00:00 +0000

Label-free single-cell 3D imaging is essential for accurate phenotyping by minimizing perturbations to native cellular states and facilitating downstream molecular analyses. Among the available modalities, 3D forward-scattering (dark-field) imaging offers the richest subcellular details but faces challenges from strong transmitted-beam interference. We present a high-throughput 3D forward-scattering imaging flow cytometry system employing optical needle-beam illumination, linear micro-mirror arrays for axial scatter detection, and spatiotemporal deconvolution algorithms. Experimental validations with microstructures, hydrogel beads, and HEK-293 cells confirm the method's capability for robust subcellular resolution at ∼400 cells/s, enabling advanced label-free cellular diagnostics and analysis. This platform enables label-free, high-content cellular analysis and is readily adaptable to integrated cell sorting and AI-driven classification, offering broad potential for biomedical...

A resource to empirically establish drug exposure records directly from untargeted metabolomics data

Mon, 15 Dec 2025 00:00:00 +0000

Despite extensive efforts, extracting medication exposure information from clinical records remains challenging. To complement this approach, here we show the Global Natural Product Social Molecular Networking (GNPS) Drug Library, a tandem mass spectrometry (MS/MS) based resource designed for drug screening with untargeted metabolomics. This resource integrates MS/MS references of drugs and their metabolites/analogs with standardized vocabularies on their exposure sources, pharmacologic classes, therapeutic indications, and mechanisms of action. It enables direct analysis of drug exposure and metabolism from untargeted metabolomics data, supporting flexible summarization at multiple ontology levels to align with different research goals. We demonstrate its application by stratifying participants in a human immunodeficiency virus (HIV) cohort based on detected drug exposures. We uncover drug-associated alterations in microbiota-derived N-acyl lipids that are not captured when stratifying...

Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity

Fri, 5 Dec 2025 00:00:00 +0000

BACKGROUND: In people with HIV who are virally suppressed with antiretroviral therapy, abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting that it might mitigate NCI in people with HIV and viral suppression. METHODS: This 6-month phase 2 randomized open-label clinical trial compared tesamorelin vs standard of care (SOC) for NCI in people with HIV who were virally suppressed and abdominally obese (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. RESULTS: Seventy-three participants were randomized 3:2 to tesamorelin or SOC (2 mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily...

Cannabis use is associated with alterations in NLRP3 inflammasome related gene expression in monocyte-derived macrophages from people living with HIV

Thu, 4 Dec 2025 00:00:00 +0000

Introduction: Human immunodeficiency virus (HIV) infection is often associated with chronic inflammation and cognitive dysfunction in people living with HIV (PWH). The nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays a crucial role in the secretion of pro-inflammatory cytokines, specifically interleukin (IL)-18 and IL-1β. Cannabis use and certain phytocannabinoids, such as cannabidiol (CBD), may provide therapeutic benefits in conditions associated with chronic inflammation. Methods: In this cross-sectional study, we investigated the relationship between cannabis use and NLRP3-related gene expression in monocyte-derived macrophages (MDMs) from PWH (n = 43) and people without HIV (PWoH; n = 22). Participants were categorized as naïve, moderate, or daily cannabis users. Donor-derived MDMs were treated with CBD (30 μM), IL-1β (20 ng/mL), or CBD + IL-1β for 24 hours to examine effects on NLRP3-related gene expression....

Association of epigenetic aging with plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation in Hispanic/Latino adults