Glycyrrhizic Acid Mitigates Haloperidol-Induced Neurotoxicity in SHSY-5Y Cells and Rats Via Activation of PI3k/Akt/Nrf2 Pathways.

Antipsychotic medications are used to treat a psychological condition called 'Schizophrenia'. However, its long-term administration causes irregular involuntary motor movements, targeting the orofacial regions. Glycyrrhizic acid (GA) is a naturally occurring triterpene saponin glycoside obtained from the roots of the Glycyrrhiza glabra (liquorice) plant and well known for its antioxidant, antiapoptotic and neuroprotective abilities.

CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs).

The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age.

Horizontal transfer and recombination fuel Ty4 retrotransposon evolution in Saccharomyces.

Horizontal transposon transfer (HTT) plays an important role in the evolution of eukaryotic genomes, however the detailed evolutionary history and impact of most HTT events remain to be elucidated. To better understand the process of HTT in closely related microbial eukaryotes, we studied Ty4 retrotransposon subfamily content and sequence evolution across the genus Saccharomyces using short- and long-read whole genome sequence data, including new PacBio genome assemblies for two S. mikatae strains.

Hepatobiliary scintigraphy and liver function changes in patients with hepatocellular carcinoma treated with Ho-radioembolization : HBS in HCC treated with holmium-166.

Background: To study the feasibility of hepatobiliary scintigraphy (HBS) to improve selection and planning of patients with hepatocellular carcinoma (HCC) treated with holmium-166 (Ho)-microspheres radioembolization.

Results: Thirty-one patients with HCC were included and treated with Ho- radioembolization as part of a prospective phase 2 study. Twenty-seven patients were eligible for analysis, 67% had a cirrhotic liver morphology on imaging, 70% had multifocal disease and 51% had bilobar disease.

Development and validation of nomograms and integrated software incorporating preoperative C-reactive protein level for prognostic prediction of nonmetastatic clear cell renal cell carcinoma: Results from the International Marker Consortium for Renal Cancer (INMARC) Registry.

Purpose: Preoperative C-reactive protein (CRP) is a valuable prognostic biomarker in nonmetastatic clear cell renal cell carcinoma (nmccRCC). Incorporation of CRP into prognostic models may improve the prediction of oncologic outcomes. Herein, we aimed to develop and validate prognostic nomograms and an integrated software incorporating preoperative CRP level in nmccRCC.

Advancing Early Detection of Alzheimer’s Disease in the Primary Care Setting in the United States.

Background: Recent advances in diagnostics have made it possible to identify early signs of the pathophysiological changes underlying Alzheimer’s Disease (AD) via blood tests. However, the use of blood‐based biomarkers (BBBMs) for the early detection of AD may be limited in primary care settings despite its potential for wide access and early detection of AD (PMID: 37295421) Therefore, there is a need to understand the barriers and facilitators of BBBM testing for AD in primary care.

Method: We employed a combination of qualitative research, advisory board, and quantitative survey to engage with clinical/scientific advisors and community‐based physicians in primary care.

Digital version of Defense Automated Neurobehavioral Assessment in South Asian Setting: Preliminary evidence from the P‐CARRS study.

Background: The Defense Automated Neurobehavioral Assessment (DANA) encompasses a suite of standardized neurocognitive screening tools designed for detecting various neurodegenerative diseases and subtle cognitive deficits. This study presents a pilot investigation into digital cognitive screening, utilizing an Android version of the DANA tests, conducted among a diverse South Asian population residing in India.

Methods: The study involved individuals aged over 50 years, nested within the ongoing population‐based longitudinal Precision‐CARRS study, representative of socio‐demographically and linguistically diverse adults from Delhi and Chennai in India.

Exercising Physiological Pathways: The Impact of Exercise on Metabolic Aging, Cellular Aging, and Inflammatory Biomarkers in All‐Cause Dementia.

Background: Physiological changes, including metabolic and cellular aging, as well as increased inflammation, occur in people living with dementia (PWD). While there is existing evidence in other populations suggesting that exercise may improve physiological outcomes, their impact in PWD remains unclear. This randomized controlled trial (RCT) aimed to assess the effects of exercise on serum levels of metabolic aging, cellular aging, and inflammatory blood biomarkers relative to usual care alone in PWD.

Digital Clock Assessment in South Asian Setting: Insights from the P‐CARRS study.

Background: Detection of presymptomatic individuals or those with subtle cognitive changes in midlife may prevent or slow the course of Alzheimer's Disease by identifying candidates for disease‐modifying treatments. Utilizing newer delivery approaches involving digital measures shows promise for cognitive phenotyping, early detection, ease of administration, and scoring, particularly in low‐resource settings. However, the feasibility of these approaches, along with their association with demographics and their effectiveness in detecting fine‐grained aspects of cognitive performance in low‐resource settings, remains unclear.

Characterizing plasma biomarkers of Alzheimer’s disease in three non‐human primate species: marmosets, titi monkeys, and capuchins.

Background: Studies of aging in non‐human primates are important to elucidate primate‐specific mechanisms underlying human aging, including pathological trajectories like Alzheimer’s disease (AD). Evidence of AD‐like brain aging has been reported across the primate order including amyloid beta (AB) deposits, but blood‐based biomarkers are less well‐studied. The goal of this project was to explore the use of validated assays for plasma biomarkers in two new non‐human primate species: coppery titi monkeys (Plecturocebus cupreus) and brown capuchins (Sapajus apella).

Neuroimaging Correlates of Alzheimer’s Disease biomarkers in a mid‐life, racially diverse high‐risk cohort.

Background: Clinicians and researchers utilize neuroimaging (NI) biomarkers of Alzheimer’s disease (AD) at an increasing rate. It is crucial that we determine whether these biomarkers generalize to underrepresented populations, particularly Black Americans (BAs), as they are 64% more likely as white individuals to develop AD. BAs may exhibit unique AD biomarker profiles across disease states, including NI biomarkers.

First Comprehensive Intranasal PET imaging of Insulin using the Aptar device in Nonhuman Primates.

Background: Insulin resistance (IR) is associated with abnormal tau‐phosphorylation and IR markers in AD brain co‐localize with neurofibrillary tangles. One strategy to overcome brain IR is to increase brain insulin is via intranasal insulin (INI) administration using specialized intranasal devices that deliver insulin to the brain. Our recent INI vs.

Mechanistic Insights of Gamma Sensory Stimulation: CSF Proteomic Analyses Reveal Changes in Myelin and Synaptic Proteins.

Background: Preclinical investigations in Alzheimer’s disease (AD) have highlighted the efficacy of gamma sensory stimulation in mitigating AD‐related pathologies. Cognito Therapeutics, Inc. (Cambridge, MA) has designed the Sensory Stimulation System for safe at‐home usage, to induce EEG‐confirmed gamma oscillations as a potential treatment for AD.

The relationship between physiological biomarkers, physical function, and fall‐risk among people living with dementia.

Background: People living with dementia (PWD) have upregulated inflammatory pathways, exaggerated metabolic aging, and cellular aging. They also have declines in physical function and heightened fall‐risk. Understanding the physiologic factors that influence physical decline and fall‐risk in PWD is vital to assess and prevent adverse health outcomes, such as future falls.

Cerebrospinal Fluid Proteomics in Down Syndrome Identifies Common and Unique Pathological Changes Compared to Late‐Onset and Autosomal Dominant Alzheimer’s Disease.

Background: Nearly all people with Down Syndrome (DS) develop Alzheimer’s dementia (AD) by the 7 decade of life. However, whether the alterations in fluid biomarker levels associated with DS follow the same pattern to those observed in other forms of AD is not well understood.

Method: We used mass spectrometry‐based proteomics to measure 1116 proteins in cerebrospinal fluid (CSF) across euploid controls (n=130), sporadic late‐onset AD (LOAD, n=89), asymptomatic DS (n=117), prodromal DS (n=57), and dementia DS (n=80) cases, and compared the protein changes observed in DS to those in LOAD and to those recently described in autosomal dominant AD (ADAD).

Health‐Related Behaviours in Octogenarians and Nonagenarians with Robust Cognitive Longevity: Progress and Initial Data from thee SuperAging Research Initiative.

Background: SuperAgers—individuals age 80+ with episodic memory performance at least as good as those 20‐30 years younger—provide a unique perspective on cognitive resilience and resistance in aging. The SuperAging Research Initiative (SRI), spearheaded by The University of Chicago and involving multiple academic partners, investigates factors underpinning robust cognitive aging. One key SRI project, leverages a fully remote data collection paradigm to: 1) discern activity patterns that characterize SuperAgers and 2) explore the 'complexity hypothesis in aging'—whether dynamic physiological responsiveness is a hallmark of exceptional cognitive aging.

Proteomic Signature of The Cerebrospinal Fluid (CSF) in Preclinical and prodromal AD: A key role for adhesion proteins.

Background: Alzheimer's Disease (AD) proteomic studies have focused on understanding the pathophysiology of AD during the late stages of AD. However, recent studies have suggested that the preclinical stage of AD represents a golden window for intervention. Yet, little is known about the influence of the cerebrospinal fluid (CSF) molecular environment on the mechanisms underlying the pathogenesis of AD during the preclinical stage.

Proteomic Analysis Resolves Distinct Molecular Signatures in Alzheimer’s Disease Brain Across Diverse Racial Groups.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non‐Hispanic White (NHW) population. To address this, Accelerating Medicines Partnership in AD (AMP‐AD) aimed to promote inclusivity in multi‐omics AD research, to unravel unique molecular signatures and pathways. The study aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial groups.

Research Lumbar Puncture Recruitment, Safety and SOPs in Black/African American and white middle‐age participants.

Background: The Wharton Lab has collected CSF for over 10 years as a primary endpoint in NIH/NIA funded longitudinal observational studies and clinical trials in cognitively normal individuals with a parental history of Alzheimer’s disease (AD). LPs provide vital data on AD risk and progression and time specific information on efficacy for clinical interventions, yet few investigators include research LPs, for fear of clinical implications, lack of specialized clinicians, and perceived unwillingness of participants to consent to LPs, particularly in minoritized participants

Method: Comprehensive data is collected on willingness to take part in LP, safety, and procedure specifics, including side effects. Twenty milliliters of CSF are obtained using fluid drip or aspiration methods.

Longitudinal Association of Perceived Stress with Cerebrospinal Fluid Alzheimer's Disease Biomarkers in a Biracial Cohort.

Background: African American (AA) persons have a higher Alzheimer's disease (AD) prevalence and report more perceived stress than White persons. Our previous cross‐sectional study (JAD, 2020, 77:843‐853) demonstrated an association between self‐reported stress levels and cerebrospinal fluid (CSF) AD biomarkers. Using a biracial cohort, the current study investigates the association between stress and longitudinal CSF AD biomarkers over time.

Association between Medical Comorbidities and White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study.

Background: Older African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease and related dementias (ADRD) compared to non‐Hispanic white (NHW) adults. AA and HA persons may also develop disease at younger ages with more rapid progression. Vascular disease, including cerebral small vessels, manifest by white matter hyperintensity (WMH) lesions, is more prevalent in AA and HA.

Alzheimer's Disease cerebrospinal fluid Biomarkers and kidney function in normal and cognitively impaired older adults.

Background: Recent Alzheimer’s disease (AD) clinical trials have used CSF biomarker levels for screening and enrollment. Preliminary evidence suggests Alzheimer’s Disease (AD) risk may be related to impaired renal function but the association of variation in levels of biomarkers commonly used AD biomarkers with kidney function is unknown.

Method: We conducted an analysis using data from participants enrolled in two research protocols at the Goizueta Alzheimer’s Disease Research Center that had simultaneous measurements of serum creatinine at the time of their Cerebrospinal fluid (CSF) collection (N=970).

Association of Plasma Alzheimer’s Disease Biomarkers with White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study.

Background: Older African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease (AD) than older non‐Hispanic white (NHW) adults. Cerebrovascular disease reflected by white matter hyperintensity (WMH) lesions on magnetic resonance imaging (MRI) may influence ADRD risk in these groups. Amyloid and tau PET data from studies of mostly NHW participants show a relationship between AD pathology and WMH lesions.

Association between Stress and White Matter Hyperintensity Volume in Diverse Populations: A HABS‐HD Study.

Background: Older African American (AA) and Hispanic American (HA) adults have a higher risk for Alzheimer’s disease and related dementias (ADRD) than older non‐Hispanic white (NHW) adults. Adverse experiences like stress and discrimination may contribute to the higher vascular disease burden observed in AA and HA persons. Cerebrovascular disease reflected by white matter hyperintensity (WMH) lesions on magnetic resonance imaging (MRI) may affect ADRD risk in older AA and HA adults.

Unraveling the earliest phases of vascular cognitive impairment and dementia by establishing a large USA CADASIL Consortium.

Background: CADASIL, linked to NOTCH3 variants, is a primary monogenic cause of vascular dementia, leading to vascular cognitive impairment and dementia (VCID) observable in early stages. The NIH‐funded USA CADASIL Consortium aims to explore CADASIL's onset and progression in the USA, crucial due to varying phenotype‐genotype associations globally. The consortium will identify biological and clinical markers across the disease spectrum, contributing to clinical trial preparations.